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: pactr.samrc.ac.za
Trial no.: PACTR202101544570971 Date of Approval: 21/01/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Prevention and treatment for covid-19 associated severe pneumonia in The Gambia: a randomized clinical trial (PaTS-COVID) COVID-19
Official scientific title Prevention and Treatment of COVID19 Associated Severe Pneumonia in The Gambia: A single blind - Randomized Trial COVID-19
Brief summary describing the background and objectives of the trial The coronavirus disease 2019 (COVID-19) has now spread to six continents. Up to 80%-85% of individuals infected with COVID-19 are asymptomatic or develop mild illness. In China, United States (US) and Europe and UK, hospitalization occurred in 10.6% - 32% of the reported cases and approximately 2% required ICU (median 7 days at ICU) . The most common diagnosis in patients with severe COVID-19 is severe pneumonia, which may be complicated by acute respiratory distress syndrome, sepsis, shock and multi organ failure. For patients progressing to severe illness, there are three different stages, in the early stages with a viral response phase that is followed by a host inflammatory response. Old age and existing comorbidities including hypertension, diabetes and chronic lung diseases increase the risk of severity and death. As the demography in Africa largely differs from high income countries, we expect that the pattern of hospitalization and deaths will differ, with higher prevalence of younger individuals than in Europe. In addition, there is hope that mortality may be lower as approximately 6% of the population is 60 years of age or older compared to 30% in Europe. However, other prevalent conditions in Africa such as malnutrition, tuberculosis, malaria or HIV, may increase the severity of the infections; although, it is still unknown if this association exists. Objectives: Patients with COVID-19 associated mild disease/moderate pneumonia (Cohort 1): 1. To evaluate the efficacy of the chosen drug in preventing progression to severe pneumonia 2. To evaluate the efficacy of prophylactic chosen drug in preventing COVID19 infection among HH contacts (both symptomatic and asymptomatic) Patients with COVID-19 associated severe pneumonia (Cohort 2): 3. To evaluate the efficacy of (adaptative selection of potential drugs including steroid or anticoagulant) in preventing clinical progression (based on a 7-point ordinal scale) or death.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PaTS COVID
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Coronavirus disease 2019
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/12/2020
Actual trial start date
Anticipated date of last follow up 30/12/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 1200
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
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 Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Cohort 1 Ivermectin and Cohort 2 Aspirin Ivermectin is 0.3-0.4mg/kg once daily Aspirin is Day 1 – 10: 150 mg once daily Ivermectin is for 3 days Aspirin is 28 days or until discharged Ivermectin Ivermectin (IVM) is an antiparasitic drug with established use as a mass drug administration agent in sub-Saharan Africa for trachoma, scabies and other parasitic infections. Evidence is accumulating for Mass Drug Administration use in disrupting malaria transmission (ongoing trial in The Gambia)16. It also has reported anti-inflammatory actions and in vitro acitivity against SARS-Co-V2 at high doses.17 There is observational study data indicating that Ivermectin may be associated with survival benefit but all studies reported to date have been non-peer reviewed, non-randomised with high risk of bias and small sample size18. Further evaluation of this potentially feasible and acceptable medication is required to establish effectiveness against SARS-CoV2 for non-severe cases and contacts. Aspirin Aspirin has anti-viral, anti-inflammatory and anti-thrombotic actions. It is licensed for the secondary prevention of cardiovascular disease and management of ischaemic heart disease and cardiac failure in addition to use as an acute antithrombotic treatment for ischaemic strokes. It is PaTS-COVID Trial: Protocol Version 1.3_17 August 2020 hypothesised to have a mitigating role in the pathogenesis of severe COVID-19 disease through multiple mechanisms. Current trials are ongoing worldwide, including a planned RCT in Nigeria and Pakistan (CRASH-19) 750
Control Group Placebo Placebo 1 (Day 1-10: 6 mg once daily) Placebo 2 (Day 1 – 10: 150 mg once daily) Placebo 1 (3 days) Placebo 2 (Until discharged) We are using an identical placebo for each of the two study drugs. 450 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Cohort 1 Inclusion Individuals ≥ 5 years of age with confirmed COVID19 mild disease or moderate pneumonia defined as: - Mild disease - Influenzae like illness, with any of the following symptoms cough, fever, headache, sore throat, nasal congestion/runny nose, body pains (myalgia), fatigue (malaise), diarrhea, abdominal pain, anorexia, nausea or vomiting without evidence of pneumonia or hypoxia - Moderate pneumonia –Clinical signs of pneumonia (fever, cough, dyspnoea, fast breathing) with no need for supplemental oxygen (oxygen saturation ≥90%% on room air or RR between 20 and 30bpm). HH members from Cohort 1 – Individuals > 5 year of age living in the same HH with the index cases from cohort 1 will be offered to participate into the study. Living in the same HH is defined as those individuals who are planning to sleep in and eat from same compound during the following 2 weeks Cohort 2 Individuals ≥12 years of age with suspected or confirmed COVID-19 associated severe pneumonia defined as signs of pneumonia (fever, cough, dyspnoea or fast breathing) plus one of: oxygen saturation (SpO2) <90% on room air OR respiratory rate > 30 breaths/minute Suspected COVID-19 disease is defined as clinically or radiologically suspected as determined by the most senior clinician available: 1. Clinically suspected Signs and symptoms of pneumonia (as defined above) AND patient living in or recent travel to region with community transmission OR close contact with known COVID-19 patient AND no alternative diagnosis to explain the clinical picture OR 2. Radiologically suspected Typical radiological signs of COVID-19 on chest X-ray or lung ultrasound Cohort 1 Pregnant women will be excluded from both Cohort 1 if the drug is IVM and . Individuals will be excluded into the study if: - Known contra-indication or allergy to study drugs Cohort 2 If the drug is Aspirin. Individuals will be excluded into the study if: - Known contra-indication or allergy to study drugs Some clinical characteristics will exclude participants from some of the severe pneumonia arms: PaTS-COVID Trial: Protocol Version 1.3_17 August 2020 o Patients already on steroids will be excluded from the dexamethasone arm if applicable o Active untreated or inactive tuberculosis for the deaxamethasone arm if applicable o Known bleeding disorder for aspirin if applicable o Prolonged QTc – excluded from azithromycin if applicable 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s) 5 Year(s) 100 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 21/09/2020 Gambia Government MRC Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Atlantic Road Fajara Fajara 220 Gambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cohort 1 Percentage of patients with COVID-19 associated mild disease/moderate pneumonia progressing within 14 days after recruitment into severe pneumonia, defined as per most recent adapted WHO definition15 as follows : Clinical signs of pneumonia plus: • Oxygen saturation (SpO2) <90% on room air OR • Respiratory rate > 30 breaths/min Note: if WHO definitions change over the course of the recruitment phase of the trial, the trial definitions will be adapted accordingly. 2. Cohort 1 HH contacts - % of HH members that get infected with COVID19 during the 14 days following recruitment (defined as those RT-PCR and IgM/IgG negative at day 1 who become positive either by RT-PCR or IgM/IgG by day 14) 3. Cohort 2 - Percentage of COVID-19 associated severe pneumonia patients meeting the criteria of failure defined as worsening their condition over a 24h period (Increase by 1 point from baseline on a 7-point ordinal scale) or who die during hospitalization. The 7-point ordinal scale consists of: 1) Not hospitalised 2) Hospitalised – not on oxygen, no longer needs medical care 3) Hospitalised – not on oxygen, needs ongoing medical care 4) Hospitalised – on or requiring supplemental oxygen given by nasal cannula or face mask to maintain SpO2 and/or respiratory rate within normal range for age 5) Hospitalised – on or requiring non-invasive ventilation or high-flow oxygen devices to maintain SpO2 and/or respiratory rate within normal range for age 6) Hospitalised – on or requiring invasive ventilation OR failure of NIV/high flow oxygen devices to maintain SpO2 and/or respiratory rate within normal range for age 7) Death Cohort 1 at day 28, Cohort 2 at discharge or death and day 28 and day 90
Secondary Outcome Cohort 1 Percentage of patients with COVID-19 associated mild disease/moderate pneumonia progressing within 14 days after recruitment into severe pneumonia, defined as per most recent adapted WHO definition15 as follows : Clinical signs of pneumonia plus: • Oxygen saturation (SpO2) <90% on room air OR • Respiratory rate > 30 breaths/min Note: if WHO definitions change over the course of the recruitment phase of the trial, the trial definitions will be adapted accordingly. 2. Cohort 1 HH contacts - % of HH members that get infected with COVID19 during the 14 days following recruitment (defined as those RT-PCR and IgM/IgG negative at day 1 who become positive either by RT-PCR or IgM/IgG by day 14) 3. Cohort 2 - Percentage of COVID-19 associated severe pneumonia patients meeting the criteria of failure defined as worsening their condition over a 24h period (Increase by 1 point from baseline on a 7-point ordinal scale) or who die during hospitalization. The 7-point ordinal scale consists of: 1) Not hospitalised 2) Hospitalised – not on oxygen, no longer needs medical care 3) Hospitalised – not on oxygen, needs ongoing medical care 4) Hospitalised – on or requiring supplemental oxygen given by nasal cannula or face mask to maintain SpO2 and/or respiratory rate within normal range for age 5) Hospitalised – on or requiring non-invasive ventilation or high-flow oxygen devices to maintain SpO2 and/or respiratory rate within normal range for age 6) Hospitalised – on or requiring invasive ventilation OR failure of NIV/high flow oxygen devices to maintain SpO2 and/or respiratory rate within normal range for age 7) Death Cohort 1 at day 28, Cohort 2 at discharge or death and day 28 and day 90
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Medical Research Council Unit The Gambia at LSHTM Atlantic Road, Fajara Fajara Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
MRCG at LSHTM Atlantic Road, Fajara Fajara Gambia
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Medical Research Council Unit The Gambia at LSHTM Atlantic Road, Fajara Fajara Gambia Research Institute
COLLABORATORS
Name Street address City Postal code Country
Ministry of Health Republic of The Gambia The Quadrangle Banjul Gambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Anna Roca Anna.Roca@lshtm.ac.uk 002204496442 Atlantic Road, Fajara
City Postal code Country Position/Affiliation
Fajara Gambia PI
Role Name Email Phone Street address
Public Enquiries Effua Usuf Effua.Usuf@lshtm.ac.uk 002207355489 Atlantic Road
City Postal code Country Position/Affiliation
Fajara Gambia Public enquiries
Role Name Email Phone Street address
Scientific Enquiries Effua Usuf Effua.Usuf@lshtm.ac.uk 002207355489 Atlantic Road
City Postal code Country Position/Affiliation
Fajara Gambia Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All patients data will be shared. Clinical Study Report,Study Protocol 24 months after analysis Open
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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