Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202007653923168 Date of Approval: 16/07/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A clinical trial comparing use of convalescent plasma therapy plus standard treatment to standard treatment alone in patients with severe COVID-19 infection
Official scientific title A randomized control trial comparing convalescent plasma therapy plus standard treatment versus standard treatment alone in patients with severe COVID-19 pneumonia at a tertiary hospital
Brief summary describing the background and objectives of the trial COVID 19 pandemic is as a result of SARs-COV 2 virus that was first reported in Wuhan, China in December 2019. As of 13 May 2020, there were over 4 million reported cases with almost 300000 fatalities. With no effective antiviral therapy and a vaccine a long way to go, use of convalescent plasma therapy has shown promising results in small pilot studies as well as against other known viruses such as MERS, SARS and H1N1 influenza. The primary objectives of this trial is to look at the safety and efficacy of convalescent plasma therapy plus standard treatment compared to standard treatment alone in patients with severe COVID 19 using the WHO 6 category ordinal scale of clinical status.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) None
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID 19
Purpose of the trial Treatment: Other
Anticipated trial start date 01/08/2020
Actual trial start date 01/08/2020
Anticipated date of last follow up 31/12/2021
Actual Last follow-up date 31/12/2021
Anticipated target sample size (number of participants) 206
Actual target sample size (number of participants) 206
Recruitment status Not yet recruiting
Publication URL Not yet sent for publication
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Convalescent plasma group 350mls of convalescent plasma transfused as a single dose in addition to standard treatment for severe Covid-19 over 4 hours The acquired ABO and rhesus compatible convalescent plasma will be transfused to the eligible new admitted Covid-19 positive ICU patient with respiratory failure. Patients will receive 350ml of convalescent plasma over 4 hours. Standard safety precautions observed during a blood transfusion will be followed. This includes accurate patient identification, monitoring patient vital signs (temperature, blood pressure, heart rate, respiratory rate), skin, urine color among others(38)(39)( see attached convalescent plasma transfusion chart). In the event of an acute transfusion reaction, standard protocol of stopping transfusion immediately and administering 10mg of chlorpheniramine and 200mg of hydrocortisone intravenously will be followed. The blood bank and principal investigator will be notified immediately. Clinical data as well as the standard laboratory and imaging studies will be collected at baseline, 1 hour, 6 hours after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment. Counselling of recipients of CP will also be done before transfusion. 103
Control Group Standard treatment None None Patient will receive standard COVID 19 treatment as per the national guidelines 103 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion criteria for donors of CP (a) Confirmation of previous infection with SARS-CoV2 by a record of RT-PCR test result. At least 2 negative RT-PCR tests after recovery (b) An interval of at least 14 days after initial illness which is assumed to be the day when the patient had a positive RT-PCR test for SARS-COV2. (c) Must meet standard criteria for whole blood donation according to Kenyan blood bank requirements and standards (age (>18yrs), weight (>50kg), collection frequency (atleast 3 months since last donation), vital signs within normal ranges, good health) in line with WHO Blood Regulators Network (BRN): Donor selection in case of pandemic situations’. (d) Non-reactivity of blood samples for transfusion transmitted infections including HIV, HBV, HCV, syphilis (for whole blood) and malaria (e) To avoid the risk of transfusion-related acute lung injury (TRALI), preference will be given to use of plasma from male donors or from female donors who have never been pregnant including abortions. This measure lowers the possibility of presence in the plasma of the antibodies to HLA or granulocyte antigens that cause TRALI. TRALI occurs within 6 h after transfusion of implicated plasma and can be severe. Inclusion Criteria for recipients of CP: 1. Confirmed Covid-19 patients with severe disease defined as oxygen saturation ≤ 93 in resting state and PaO2/FiO2 ≤300mmHg who have understood and signed the written informed consent form. If patients are eligible but are too sick to give consent, their legally authorized close relatives will consent for them. 2. Age ≥18 years, gender unlimited. 2 Exclusion criteria for donors of CP a) Patients aged less than 18 years of age (18 years is the legal consent age in Kenya) b) Symptomatic patients with COVID-19 c) Patients with fever of unknown origin d) Patients who don’t meet Kenyan standards of blood donation e.g anemic patients, underweight (less than 50kg), chronic diseases such as HIV, hepatitis B and C, cancers, uncontrolled hypertension etc. e) Females who have given birth or had an abortion due to high risk of TRALI f) Patients who decline or are unable to give informed consent to donate CP. Exclusion Criteria for recipients of CP: • History of allergic reaction to blood or blood products • Participation in other clinical trials. • Religious reasons such as Jehovah witnesses’ practitioners who decline blood/blood products. • Refusal to give informed consent by the patient or next of kin • Known IgA deficiency • Medical conditions in which receipt of 350mL volume may be detrimental to the patient (e.g., decompensated congestive heart failure, renal failure) • Females who are pregnant or breast feeding 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/07/2020 Kenyatta University Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
43844 Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome a) To evaluate safety of convalescent plasma therapy in patients with severe Covid-19. b) To evaluate efficacy of convalescent plasma therapy with standard treatment versus standard treatment alone with respect to time to clinical improvement (TTCI) [Time Frame: up to 28 days]. TTCI is defined as the time (in days) from initiation of study treatment (active or standard care) until a decline of two categories from admission status on a six-category ordinal scale of Clinical status which ranges from 1 (discharged) to 6 (death)(35). Six-category ordinal scale: 6. Death; 5. ICU, requiring IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula. Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, 6hrs, day 1, 3, 7, 14, 28 of hospital stay after enrollment.
Secondary Outcome • a) To compare duration of severe illness, based on SOFA score, between patients enrolled in the intervention and control groups assessed by the ordinal scale on days 7, 14, 21, and 28. b) To compare the proportion of patients requiring oxygen supplementation between the intervention and control groups up to 28 days. c) To compare the proportion of patients on mechanical ventilation between the intervention and control groups up to 28 days. d) To determine the mean PaO2/FiO2 between the intervention and control groups up to 28 days. e) To determine time to negative SARS-COV2 RT-PCR test in respiratory tract specimens between the intervention and control groups up to 28 days f) To determine the length of ICU stay(days) between the intervention and control groups up to 28 days. g) To determine length of hospital stay (days) between the intervention and control groups up to 28 days. h) To determine all-cause mortality between the intervention and control groups up to 28 days. Days 7, 14, 21, and 28 based on SOFA score
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenyatta University Teaching Referral and Research Hospital 7674 Nairobi 00100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Kenyatta University Teaching Referral and Research Hospital 7674 Nairobi 00100 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kenyatta University Teaching Referral and Research Hospital 7674 Nairobi 00100 Kenya Hospital
COLLABORATORS
Name Street address City Postal code Country
Dr Sam Aketch 43640 Nairobi 00100 Kenya
Dr Marion Kiguoya Njau 7674 Nairobi 00100 Kenya
Dr Kimondo Mutambuki 7674 Nairobi 00100 Kenya
Dr Peter Karuiki Ngugi 7674 Nairobi 00100 Kenya
Dr Sultana Sherman 7674 Nairobi 00100 Kenya
Dr mary Mwangi 7674 Nairobi 00100 Kenya
Prof Olive Mugenda 7674 Nairobi 00100 Kenya
Dr Ifrah Hersi 7674 Nairobi 00100 Kenya
Dr Diane Otieno 7674 Nairobi 00100 Kenya
Dr Maureen Nganga 7674 Nairobi 00100 Kenya
Dr Idris Chikophe Nairobi 00100 Kenya
Mercy Kahare 7674 Nairobi 00100 Kenya
Mr Wilfred Gatua 7674 Nairobi 00100 Kenya
Dr John Kaumba Nzioka 7674 Nairobi 00100 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Isaac Adembesa kadembesa@yahoo.com +254720949430 7674
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Consultant Cardiac Anaesthesiologist
Role Name Email Phone Street address
Scientific Enquiries Samuel Akech sakech@kemri-wellcome.org +254721339090 43640
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Senior researcher KEMRI Wellcome Trust
Role Name Email Phone Street address
Public Enquiries Marion Kiguoya Njau marionwangui2002@gmail.com +254722877863 7674
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Deputy Director Research
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Use of convalescent plasma therapy in COVID-19 is an experimental therapy. To add to the growing evidence which hopefully will shape use of convalescent plasma therapy in this pandemic, we intend to share our protocol and results that hopefully will form part of a meta-analysis on this subject. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol August 2020 to December 2021 Access to this data will be controlled and the principal investigator will decide ( in consultation with co-investigators) who to grant access to the data
URL Results Available Results Summary Result Posting Date First Journal Publication Date
None No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 14/07/2020 edit A randomized control trial comparing convalescent plasma therapy to standard treatment in patients with severe COVID 19 pneumonia at a tertiary hospital A randomized control trial comparing convalescent plasma therapy to standard treatment in patients with severe COVID-19 pneumonia at a tertiary hospital
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 14/07/2020 edit to include max age of 80 years Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s) Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Acronym 15/07/2020 None None
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 15/07/2020 None 01 Aug 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 15/07/2020 None 31 Dec 2021
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Publication URL 15/07/2020 None Not yet sent for publication
Section Name Field Name Date Reason Old Value Updated Value
Study Design Allocation concealment 15/07/2020 Advise from ethics committee Central randomisation by phone/fax Numbered containers
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 15/07/2020 Advise from ethics committee Experimental Group, Convalescent plasma group, 350mls given once, over 4 hours, The acquired convalescent plasma will be transfused to the eligible new admitted Covid 19 positive ICU patient with respiratory failure after ABO and Rhesus match. Patients will receive 350ml of convalescent plasma over 4 hours. Standard safety precautions observed during a blood transfusion will be followed. In the event of an acute transfusion reaction, the blood bank and principal investigator will be notified immediately. Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment., 103, Experimental Group, Convalescent plasma group, 350mls given once, over 4 hours, The acquired convalescent plasma will be transfused to the eligible new admitted Covid 19 positive ICU patient with respiratory failure after ABO and Rhesus match. Patients will receive 350ml of convalescent plasma over 4 hours. Standard safety precautions observed during a blood transfusion will be followed. In the event of an acute transfusion reaction, the blood bank, chairman of ethics committee and principal investigator will be notified immediately. Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment., 103,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 15/07/2020 None Control Group, Standard treatment, None, None, Patient will receive standard COVID 19 treatment as per the national guidelines, 103, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 15/07/2020 Spacing • Viral pneumonia with other viruses besides COVID-19. • Patients are not suitable for Convalescent Plasma Therapy e.g. history of allergic reaction to blood or blood products • Participation in other studies. • Other circumstances in which the investigator determined that the patient is not suitable for the clinical trial e.g. Jehovah witnesses • Refusal to give informed consent by Donor and/or Patient or next of kin • Known IgA deficiency • Medical conditions in which receipt of 350mL volume may be detrimental to the patient (e.g., decompensated congestive heart failure) • Females who are pregnant or breast feeding. • Viral pneumonia with other viruses besides COVID-19. • Patients are not suitable for Convalescent Plasma Therapy e.g. history of allergic reaction to blood or blood products • Participation in other studies. • Other circumstances in which the investigator determined that the patient is not suitable for the clinical trial e.g. Jehovah witnesses • Refusal to give informed consent by Donor and/or Patient or next of kin • Known IgA deficiency • Medical conditions in which receipt of 350mL volume may be detrimental to the patient (e.g., decompensated congestive heart failure) • Females who are pregnant or breast feeding.
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 15/07/2020 Added funding source Kenyatta University Teaching Referral and Research Hospital, 7674, Nairobi, 00100, Kenya, Hospital,
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 15/07/2020 Added collaborator Dr Marion Kiguoya Njau, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 15/07/2020 Added collaborator Dr Kimondo Mutambuki, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 15/07/2020 Added collaborators Dr Peter Karuiki Ngugi, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 15/07/2020 Added collaborator Dr Sultana Sherman, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 15/07/2020 Added collaborator Dr mary Mwangi, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 15/07/2020 Added postal code Public Enquiries, Marion, Kiguoya Njau, Dr., marionwangui2002@gmail.com, , +254722877863, 7674, Nairobi, , Kenya, Deputy Director Research Public Enquiries, Marion, Kiguoya Njau, Dr., marionwangui2002@gmail.com, , +254722877863, 7674, Nairobi, 00100, Kenya, Deputy Director Research
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 15/07/2020 Undecided No Undecided
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 16/07/2020 Missing figure 206
Section Name Field Name Date Reason Old Value Updated Value
Study Design Allocation concealment 16/07/2020 Addition from ethics committee Numbered containers Sealed opaque envelopes
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 16/07/2020 Additional information Experimental Group, Convalescent plasma group, 350mls of convalescent plasma transfused as a single dose, over 4 hours, The acquired convalescent plasma will be transfused to the eligible new admitted Covid 19 positive ICU patient with respiratory failure after ABO and Rhesus match. Patients will receive 350ml of convalescent plasma over 4 hours. Standard safety precautions observed during a blood transfusion will be followed. In the event of an acute transfusion reaction, the blood bank, chairman of ethics committee and principal investigator will be notified immediately. Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment., 103,
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 16/07/2020 Rephrased the inclusion criteria 1. Relatives/Patients of Covid 19 positive patients who have understood and signed the informed consent; 2. Age ≥18 years, gender unlimited; 3. Patients diagnosed with acute severe Covid 19 pneumonia: Laboratory confirmed infection with Covid 19. At least one of the following conditions should be met: • Respiratory distress defined as oxygen saturation ≤ 90% in resting state and PaO2/FiO2 ≤300mmHg; 1. Covid 19 Patients or relatives of Covid 19 positive patients who have understood and signed the informed consent; 2. Age ≥18 years, gender unlimited; 3. Patients diagnosed with acute severe Covid 19 pneumonia: Laboratory confirmed infection with Covid 19. At least one of the following conditions should be met: • Respiratory distress defined as oxygen saturation ≤ 90% in resting state and PaO2/FiO2 ≤300mmHg;
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/07/2020 Uploaded Ethics approval letter TRUE, Kenyatta University Ethics Review Committee, 43844, Nairobi, 00100, Kenya, , 10 Jul 2020, +2548710901, chairman.kuerc@ku.ac.ke, 11047_11525_4737.pdf TRUE, Kenyatta University Ethics Review Committee, 43844, Nairobi, 00100, Kenya, , 10 Jul 2020, +2548710901, chairman.kuerc@ku.ac.ke, 11047_11525_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 16/07/2020 Requirement by WHO Undecided Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 16/07/2020 Requirement by WHO Use of convalescent plasma therapy in COVID-19 is an experimental therapy. To add to the growing evidence which hopefully will shape use of convalescent plasma therapy in this pandemic, we intend to share our protocol and results that hopefully will form part of a meta-analysis on this subject.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 16/07/2020 Additional information August 2020 to December 2020
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 16/07/2020 Additional information Access to this data will be controlled and the principal investigator will decide ( in consultation with co-investigators) who to grant access to the data
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 16/07/2020 None None
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 16/07/2020 Additional information Study Protocol, Statistical Analysis Plan, Informed Consent Form, Clinical Study Report, Analytic Code
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Public title 19/08/2020 Suggestion from PPB A clinical trial comparing use of convalescent plasma therapy to standard therapy in patients with severe COVID-19 infection A clinical trial comparing use of convalescent plasma therapy plus standard treatment to standard treatment alone in patients with severe COVID-19 infection
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 19/08/2020 Suggestion from PPB A randomized control trial comparing convalescent plasma therapy to standard treatment in patients with severe COVID-19 pneumonia at a tertiary hospital A randomized control trial comparing convalescent plasma therapy plus standard treatment versus standard treatment alone in patients with severe COVID-19 pneumonia at a tertiary hospital
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 19/08/2020 PPB COVID 19 pandemic is as a result of SARs-COV 2 virus that was first reported in Wuhan, China in December 2019. As of 13 May 2020, there were over 4 million reported cases with almost 300000 fatalities. With no effective antiviral therapy and a vaccine a long way to go, use of convalescent plasma therapy has shown promising results in small pilot studies as well as against other known viruses such as MERS, SARS and H1N1 influenza. The primary objective of this trial is to look at the efficacy of convalescent plasma therapy compared to standard treatment against COVID 19 using the WHO 6 category ordinal scale of clinical status. COVID 19 pandemic is as a result of SARs-COV 2 virus that was first reported in Wuhan, China in December 2019. As of 13 May 2020, there were over 4 million reported cases with almost 300000 fatalities. With no effective antiviral therapy and a vaccine a long way to go, use of convalescent plasma therapy has shown promising results in small pilot studies as well as against other known viruses such as MERS, SARS and H1N1 influenza. The primary objectives of this trial is to look at the safety and efficacy of convalescent plasma therapy plus standard treatment compared to standard treatment alone in patients with severe COVID 19 using the WHO 6 category ordinal scale of clinical status.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial phase 19/08/2020 PPB Phase-2 Phase-3
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 19/08/2020 Suggestion from PPB 1. Covid 19 Patients or relatives of Covid 19 positive patients who have understood and signed the informed consent; 2. Age ≥18 years, gender unlimited; 3. Patients diagnosed with acute severe Covid 19 pneumonia: Laboratory confirmed infection with Covid 19. At least one of the following conditions should be met: • Respiratory distress defined as oxygen saturation ≤ 90% in resting state and PaO2/FiO2 ≤300mmHg; Inclusion criteria for donors of CP (a) Confirmation of previous infection with SARS-CoV2 by a record of RT-PCR test result. At least 2 negative RT-PCR tests after recovery (b) An interval of at least 14 days after initial illness which is assumed to be the day when the patient had a positive RT-PCR test for SARS-COV2. (c) Must meet standard criteria for whole blood donation according to Kenyan blood bank requirements and standards (age (>18yrs), weight (>50kg), collection frequency (atleast 3 months since last donation), vital signs within normal ranges, good health) in line with WHO Blood Regulators Network (BRN): Donor selection in case of pandemic situations’. (d) Non-reactivity of blood samples for transfusion transmitted infections including HIV, HBV, HCV, syphilis (for whole blood) and malaria (e) To avoid the risk of transfusion-related acute lung injury (TRALI), preference will be given to use of plasma from male donors or from female donors who have never been pregnant including abortions. This measure lowers the possibility of presence in the plasma of the antibodies to HLA or granulocyte antigens that cause TRALI. TRALI occurs within 6 h after transfusion of implicated plasma and can be severe. Inclusion Criteria for recipients of CP: 1. Confirmed Covid-19 patients with severe disease defined as oxygen saturation ≤ 93 in resting state and PaO2/FiO2 ≤300mmHg who have understood and signed the written informed consent form. If patients are eligible but are too sick to give consent, their legally authorized close relatives will consent for them. 2. Age ≥18 years, gender unlimited.
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 19/08/2020 Suggestion from PPB • Viral pneumonia with other viruses besides COVID-19. • Patients are not suitable for Convalescent Plasma Therapy e.g. history of allergic reaction to blood or blood products • Participation in other studies. • Other circumstances in which the investigator determined that the patient is not suitable for the clinical trial e.g. Jehovah witnesses • Refusal to give informed consent by Donor and/or Patient or next of kin • Known IgA deficiency • Medical conditions in which receipt of 350mL volume may be detrimental to the patient (e.g., decompensated congestive heart failure) • Females who are pregnant or breast feeding. 2 Exclusion criteria for donors of CP a) Patients aged less than 18 years of age (18 years is the legal consent age in Kenya) b) Symptomatic patients with COVID-19 c) Patients with fever of unknown origin d) Patients who don’t meet Kenyan standards of blood donation e.g anemic patients, underweight (less than 50kg), chronic diseases such as HIV, hepatitis B and C, cancers, uncontrolled hypertension etc. e) Females who have given birth or had an abortion due to high risk of TRALI f) Patients who decline or are unable to give informed consent to donate CP. Exclusion Criteria for recipients of CP: • History of allergic reaction to blood or blood products • Participation in other clinical trials. • Religious reasons such as Jehovah witnesses’ practitioners who decline blood/blood products. • Refusal to give informed consent by the patient or next of kin • Known IgA deficiency • Medical conditions in which receipt of 350mL volume may be detrimental to the patient (e.g., decompensated congestive heart failure, renal failure) • Females who are pregnant or breast feeding
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 19/08/2020 Suggestion from PPB Primary Outcome, To determine Time to Clinical Improvement (TTCI) [Time Frame: up to 28 days]. TTCI is defined as the time (in days) from initiation of study treatment (active or standard care) until a decline of two categories from admission status on a six-category ordinal scale of Clinical status which ranges from 1 (discharged) to 6 (death) (7). Six-category ordinal scale: 6. Death; 5. ICU, requiring IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula , Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment. Primary Outcome, a) To evaluate safety of convalescent plasma therapy in patients with severe Covid-19. b) To evaluate efficacy of convalescent plasma therapy with standard treatment versus standard treatment alone with respect to time to clinical improvement (TTCI) [Time Frame: up to 28 days]. TTCI is defined as the time (in days) from initiation of study treatment (active or standard care) until a decline of two categories from admission status on a six-category ordinal scale of Clinical status which ranges from 1 (discharged) to 6 (death)(35). Six-category ordinal scale: 6. Death; 5. ICU, requiring IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula. , Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, 6hrs, day 1, 3, 7, 14, 28 of hospital stay after enrollment.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 19/08/2020 Suggestion from PPB Secondary Outcome, • Clinical status assessed by the ordinal scale on days 7, 14, 21, and 28[ Time Frame: up to 28 days] based on SOFA score • The differences in oxygen intake methods [Time Frame: up to 28 days] 1. No need for supplemental oxygenation 2. Nasal catheter oxygen inhalation 3. Mask oxygen inhalation 4. Noninvasive ventilator oxygen supply 5. Invasive ventilator oxygen supply. • Duration (days) of supplemental oxygenation [Time Frame: up to 28 days] • Duration (days) of mechanical ventilation [Time Frame: up to 28 days] • The mean PaO2/FiO2 [Time Frame: up to 28 days] • Time to Covid 19 negativity in respiratory tract specimens [every 3 days] [Time Frame: up to 28 days] • Length of ICU (days) [Time Frame: up to 28 days] • Length of hospital stay (days) [ Time Frame: up to 28 days] • All-cause mortality [Time Frame: up to 28 days] , Days 7, 14, 21, and 28 based on SOFA score Secondary Outcome, • a) To compare duration of severe illness, based on SOFA score, between patients enrolled in the intervention and control groups assessed by the ordinal scale on days 7, 14, 21, and 28. b) To compare the proportion of patients requiring oxygen supplementation between the intervention and control groups up to 28 days. c) To compare the proportion of patients on mechanical ventilation between the intervention and control groups up to 28 days. d) To determine the mean PaO2/FiO2 between the intervention and control groups up to 28 days. e) To determine time to negative SARS-COV2 RT-PCR test in respiratory tract specimens between the intervention and control groups up to 28 days f) To determine the length of ICU stay(days) between the intervention and control groups up to 28 days. g) To determine length of hospital stay (days) between the intervention and control groups up to 28 days. h) To determine all-cause mortality between the intervention and control groups up to 28 days. , Days 7, 14, 21, and 28 based on SOFA score
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Prof Olive Mugenda, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Dr Ifrah Hersi, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Dr Diane Otieno, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Dr Maureen Nganga, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Dr Idris, Chikophe, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Mercy Kahare, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Mr Wilfred Gatua, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 19/08/2020 PPB Dr John Kaumba Nzioka, 7674, Nairobi, 00100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 19/08/2020 PPB August 2020 to December 2020 August 2020 to December 2021
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 19/08/2020 Suggestion from PPB Experimental Group, Convalescent plasma group, 350mls of convalescent plasma transfused as a single dose, over 4 hours, The acquired convalescent plasma will be transfused to the eligible new admitted Covid 19 positive ICU patient with respiratory failure after ABO and Rhesus match. Patients will receive 350ml of convalescent plasma over 4 hours. Standard safety precautions observed during a blood transfusion will be followed. In the event of an acute transfusion reaction, the blood bank, chairman of ethics committee and principal investigator will be notified immediately. Clinical data as well as the standard laboratory studies will be collected at baseline, 1 hour after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment., 103, Experimental Group, Convalescent plasma group, 350mls of convalescent plasma transfused as a single dose in addition to standard treatment for severe Covid-19, over 4 hours, The acquired ABO and rhesus compatible convalescent plasma will be transfused to the eligible new admitted Covid-19 positive ICU patient with respiratory failure. Patients will receive 350ml of convalescent plasma over 4 hours. Standard safety precautions observed during a blood transfusion will be followed. This includes accurate patient identification, monitoring patient vital signs (temperature, blood pressure, heart rate, respiratory rate), skin, urine color among others(38)(39)( see attached convalescent plasma transfusion chart). In the event of an acute transfusion reaction, standard protocol of stopping transfusion immediately and administering 10mg of chlorpheniramine and 200mg of hydrocortisone intravenously will be followed. The blood bank and principal investigator will be notified immediately. Clinical data as well as the standard laboratory and imaging studies will be collected at baseline, 1 hour, 6 hours after dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment. Counselling of recipients of CP will also be done before transfusion., 103,