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.: PACTR202106466447805 Date of Approval: 22/06/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia
Official scientific title A Randomized Double-blind Placebo-controlled Study to Evaluate the efficacy and Safety of Tocilizumab in Hospitalized Patients with COVID-19 Pneumonia
Brief summary describing the background and objectives of the trial There are currently no drugs licensed for the treatment of patients with COVID-19. Given the results of available data, Tocilizumab, along with standard of care (SOC) treatment, could provide benefit, offering the potential to treat COVID-19 Pneumonia in hospitalized populations more effectively than current Standard Of Care alone. Extensive safety data has previously been generated on the use of Tocilizumab in other indications e.g. for rheumatoid arthiritis. Therefore, this study will look at comparing a combination of Tocilizumab with Standard Of Care to assess safety and efficacy of Tocilizumab in hospitalized patients with COVID-19 pneumonia, and this rationale is justified to address the high unmet need and burden of disease in this severely ill population for which there is no current known better treatment options. Primary Outcome Measures : - Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28 [ Time Frame: Up to Day 28 ] Secondary Outcome Measures : 1)Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status [ Time Frame: Up to Day 28 ] 2) Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) [ Time Frame: Up to Day 28 ] 3) Mortality Rate by Day 28 [ Time Frame: Up to Day 28 ] 4) Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen) [ Time Frame: Up to Day 28 ] 5) Percentage of Participants with Adverse Events [ Time Frame: Up to Day 60 ] 6) Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection [ Time Frame: Up to Day 60 ] 7) Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline) [ Time Frame: Up to Day 60 ]
Type of trial RCT
Acronym (If the trial has an acronym then please provide) EMPACTA
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID19 Pneumonia
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/06/2020
Actual trial start date 14/05/2020
Anticipated date of last follow up 30/09/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 379
Actual target sample size (number of participants) 379
Recruitment status Closed to recruitment,follow-up continuing
Publication URL https://pubmed.ncbi.nlm.nih.gov/33332779/
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 Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax 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 Tocilizumab Patients assigned to the TCZ arm will receive one infusion of TCZ 8 mg/kg, with a maximum dose of 800 mg, and patients assigned to the placebo arm will receive one infusion of placebo One infusion One infusion of Tocilizumab 8mg/kg with a maximum dose of 800mg 253
Control Group Placebo One infusion One infusion Normal Saline 126 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria Hospitalized COVID-19 pneumonia confirmed by a positive polymerase chain reaction (PCR) of any specimen and radiographic imaging SpO2 < 94% while on ambient air Exclusion Criteria Known severe allergic reactions to TCZ or other monoclonal antibodies Require continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or invasive mechanical ventilation Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments Immunocompromised (besides well-controlled HIV) or on immunosuppressive therapy (except for steroids for COVID), advanced cancer Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months Participating in another interleukin (IL)-6 antagonist clinical trial or other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 10 x upper limit of normal (ULN) detected within 24 hours at screening (according to local laboratory reference ranges) Absolute neutrophil count (ANC) < 1000/uL at screening (according to local laboratory reference ranges) Platelet count < 50,000/uL at screening (according to local laboratory reference ranges) Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination Treatment with an investigational drug within 5 half lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medical Monitor) Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study Any history of Diverticulitis or GI perforation Use of systemic corticosteroids unless on a stable chronic dose 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) 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 01/07/2020 Institutional Ethics Review Committee IREC The AgaKhan University Kenya
Ethics Committee Address
Street address City Postal code Country
3rd Parklands Avenue, Off Limuru Road, Nairobi Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary Outcome Measures : Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28 Up to Day 28
Secondary Outcome Secondary Outcome Measures : Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status [ Time Frame: Up to Day 28 ] Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) [ Time Frame: Up to Day 28 ] Mortality Rate by Day 28 [ Time Frame: Up to Day 28 ] Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen) [ Time Frame: Up to Day 28 ] Percentage of Participants with Adverse Events [ Time Frame: Up to Day 60 ] Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection [ Time Frame: Up to Day 60 ] Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline) [ Time Frame: Up to Day 60 ] Up to Day 60
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
AgaKhan University Hospital Nairobi 3rd Parklands Avenue, off Limuru Road, R 0. Box 30270, GPO 00100, Nairobi, Kenya Nairobi 00100 Kenya
University of the Free State Bloemfontain Bloemfontain 9301 South Africa
George Provincial Hospital George George 6259 South Africa
Peermed Clinical Trial Centre Kempton Park Kempton Park 1619 South Africa
Mzansi Ethical Research Centre Middelburg Middelburg 1055 South Africa
Milpark Hospital Parktown West Parktown West 2196 South Africa
Hospital Militar Central Jesus Maria Lima 11 Peru
Hospital General de Culiacan Culiacan Culiacan 80230 Mexico
Hospital E Maternidade Celso Pierro PUCCAMP Campinas Sao Paolo 13060-904 Brazil
Sentara Medical Group Virginia Beach Virginia 23462 United States of America
McAllen Medical Centre McAllen Texas 78503 United States of America
St. Barnabas Hospital Bronx New York 10457 United States of America
Jamaica Hospital Medical Center Jamaica New York 11418 United States of America
Henry Ford Health System Detroit Michigan 48202 United States of America
University of Miami Pulmonary Miami Florida 33125 United States of America
El Centro Regional Medical Center El Centro California 92243 United States of America
Univ of Arizona College of Medicine Tuscon Arizona 85724 United States of America
FUNDING SOURCES
Name of source Street address City Postal code Country
Genentech Inc. 1 DNA Way South San Francisco San Francisco 94080 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Genentech Inc 1 DNA Way South Sanfrancisco San Francisco 98020 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Beatrice Nyawira beatrice.nyawira@roche.com +254733440526 The Atrium Chaka Road
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Medical Director East Africa
Role Name Email Phone Street address
Principal Investigator Reena Shah reena.shah@aku.edu +254203662117 AgaKhan University Hospital Nairobi 3rd Parklands Avenue off Limuru Road
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Infectious Disease Department
Role Name Email Phone Street address
Public Enquiries Huwaida Bulhan huwaida.bulhan@roche.com +254780888997 The Atrium Chaka Road
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Clinical Operations Lead SubSahara Africa
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes ClinicalTrials.gov Identifier: NCT04372186 NEJM publication link - https://pubmed.ncbi.nlm.nih.gov/33332779/ Study Protocol Annual study update NEJM publication link - https://pubmed.ncbi.nlm.nih.gov/33332779/
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://pubmed.ncbi.nlm.nih.gov/33332779/ Yes 21/06/2021 07/01/2021
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 21/06/2021
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information