Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Inclusion criteriaThe inclusion criteria are as follows:
Exclusion criteriaThe exclusion criteria are as follows:
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
The intervention is described as follows for the experimental and control groups:
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Primary outcome measure
Secondary outcome measures:The secondary outcome measures are the following:
Participant timeline {13}
Process | Screening/baseline/randomization | Treatment phase | Follow-up phase | ||
---|---|---|---|---|---|
B/L/D0 | D1–D10 | D14 ±1 | D21 ±3 | D28 ±3 | |
Inclusion/exclusion criteria | X | ||||
Written informed consent | X | ||||
Demographics | X | ||||
Assessment of concomitant chronic diseases | X | ||||
Efficacy/safety assessment | |||||
ECG | X | X | |||
Chest imaging | X | X (only on D10) | X | ||
Vital signs (body temperature, heart rate, blood pressure, breathing rate, oxygen saturation, etc.) | X | X | X | X | X |
Clinical symptoms assessment (fever, cough, diarrhea, dyspnea) | X | X | X | X | X |
Primary endpoint assessment | X | X | X | X | X |
Adverse events | X | X | X | X | X |
Laboratory test | |||||
Diagnosis (clinical diagnosis, antibody diagnosis, or pathogen diagnosis) | X | ||||
Whole blood count (sampling time) | X | X (only on D3, D7, and D10) | |||
Coagulation routine (sampling time) | X | X (only on D3, D7, and D10) | |||
Kidney and liver function tests (sampling time) | X | X (only on D3, D7, and D10) | |||
Arterial blood gas analysis | X | ||||
Pregnancy test (urine/blood, for women of childbearing age only) | X | ||||
Nasopharyngeal/ oropharyngeal swab | X | X | X | X | X |
Lower respiratory tract specimen (sputum/tracheal aspirate/bronchial alveolar lavage fluid) if available | X | X | X | X | X |
Feces/anal swabs | X | X | X | X | X |
Pharmacokinetic sampling (approximately 4 ml whole blood) | X (only on D1, D3, D7 [as needed], and D10) | ||||
Interventions | |||||
Remdesivir/placebo | X | ||||
Concomitant medications (record only) | X | X | X | X | X |
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded? {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Confidentiality {27}
Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
3.18.2. Interim analyses {21b}
3.18.3. Methods for additional analyses (e.g. subgroup analyses) {20b}
3.18.4. Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
3.18.5. Plans to give access to the full protocol, participant-level data, and statistical code {31c}
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
3.19.1.2. Trial steering committee
- Chen Wang, President of Peking Union Medical College
- Bin Cao (China-Japan Friendship Hospital), deputy team leader of Novel Coronavirus Pneumonia (NCP) Group
- Dingyu Zhang (Jin Yin-tan Hospital), Director of NCP Designated Hospital.
- Ke Wang, Director of Institute of Medicine, Chinese Academy of Medical Sciences.
Trial operation committee
Trial monitoring
Data management team
Clinical research organization
Composition of the data monitoring committee, its role and reporting structure {21a}
Data monitoring committee (DMC) members
Name | Role | Position |
---|---|---|
Jieming Qu | Chair | Professor of Respiratory Medicine & President, Ruijin Hospital Shanghai Jiao Tong University School of Medicine |
Weichung Joe Shih | Member | Director of Biometrics Division of the Cancer Institute of New Jersey, Rutgers University |
Rob Fowler | Member | Senior scientist, Evaluative Clinical Sciences, Trauma, Emergency & Critical Care Research Program, Sunnybrook Research Institute, Toronto, Canada |
Rory Collins | Member | Head, Nuffield Department of Population Health, University of Oxford, UK |
Chen Yao | Member | Biometrics Division of Peking University |
Adverse event reporting and harms {22}
Frequency and plans for auditing trial conduct {23}
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
Dissemination plans {31a}
Discussion
Trial status
Acknowledgements
Administrative information
Title {1} | A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy and Safety of Intravenous Remdesivir in Adult Patients With Severe Pneumonia caused by COVID-19 virus Infection |
Trial registration {2a and 2b} | NCT04257656 |
Protocol version {3} | Version 3.0 09 February 2020 |
Funding {4} | Funded by: • Emergency project for novel coronavirus pneumonia of the Ministry of Science and Technology (2020YFC0841300) • Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS 2018-I2M-1-003) • National Science Grant for Distinguished Young Scholars (81425001/H0104) • The National Key Research and Development Program of China (2018YFC1200102) • The Beijing Science and Technology Project (Z19110700660000) • National Mega-projects for Infectious Diseases in China (2017ZX10103004 and 2018ZX10305409). Other support: • China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical Limited, Ping An Insurance (Group), New Sunshine Charity Foundation, International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) • NIHR Senior Research Fellowship (TJ: 2015-08-001) |
Author details {5a} | Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China Jin Yin-tan Hospital, Wuhan, Hubei Province, China; Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, Hubei Province, China; Wuhan Lung Hospital, Wuhan, Hubei Province, China; The Central Hospital of Wuhan, Wuhan, Hubei Province, China; Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China; Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, Hubei Province, China; Wuhan First Hospital, Wuhan, Hubei Province, China; Wuhan Third Hospital, Wuhan, Hubei Province, China; Wuhan Fourth Hospital, Wuhan, Hubei Province, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China; Lancaster University, Lancaster, UK; University of Virginia School of Medicine, Charlottesville, VA, USA; University of Oxford, Oxford, UK; Peking Union Medical College, Beijing, China |
Name and contact information for the trial sponsor {5b} | China-Japan Friendship Hospital, Beijing, People’s Republic of China |
Role of sponsor {5c} | The study sponsor and funders had no role in study design; collection, management, analysis, or interpretation of data; writing of the report; or the decision to submit the report for publication |