E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19 |
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E.1.1.1 | Medical condition in easily understood language |
Preventing breathing complications in patients having surgery and at risk of Coronavirus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10035664 |
E.1.2 | Term | Pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003083 |
E.1.2 | Term | ARDS |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective
To provide reliable estimates of the effect of study treatments on postoperative pulmonary complications during the COVID-19 pandemic. |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of study treatments on: -Post-operative proven COVID-19 pulmonary complications -Overall SARS-CoV-2 infected rate -Duration of intensive care and total hospital stay -Pulmonary function in keeping with WHO Solidarity Trial outcome scale -Safety and tolerability of study treatments
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Testing and criteria for diagnosis COVID-19 is likely to rapidly evolve over the course of this trial and will vary internationally. Therefore, the following pragmatic definitions will be applied: • Confirmed positive test for COVID-19: either a laboratory test (performed according to each participating hospital’s local protocols) or a computed tomography (CT) thorax scan (based on individual radiologist interpretation and diagnosis) that confirms COVID-19 diagnosis. • Confirmed negative test for COVID-19: a laboratory test (performed according to each participating hospital’s local protocols) that is negative for COVID-19 diagnosis.
Patients are eligible for the study if ALL of the following apply: -Aged 18 years or above -Planned to undergo any type of elective or emergency inpatient surgery requiring general or regional anaesthesia (such as vulnerable patients undergoing surgery for a fractured neck of femur) -Asymptomatic of COVID-19, including patients with: those not tested, negative test results, postive test but no symptoms -Able to provide informed patient consent
The eligibility criteria may change over time to reflect new diagnostic tests or changing epidemiology. This will be reviewed regularly by the Trial Management Group and Data Monitoring Committee. For example, if routine serological screening before surgery becomes feasible during the course of the trial in any participating hospital, only seronegative patients may be eligible for the trial. |
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E.4 | Principal exclusion criteria |
Patients are not eligible for the study if ANY of the following apply:
--Procedures under local anaesthesia -Symptomatic COVID-19 infection (by confirmed COVID-19 test or a clinical diagnosis); these patients will be eligible for the RECOVERY trial. -Existing regular preoperative treatment with trial drugs -Known history of adverse reaction/contraindication to trial drugs -Pregnancy (including caesarean section)
It is anticipated that very few patients listed for surgery will have symptomatic COVID-19 infection at the time of surgery, and although any such patients will be excluded from this trial, they will be eligible for the parallel RECOVERY trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Trial outcomes will only be based on routinely available data. Patients will not undergo any additional investigations for trial purposes.
Primary outcome measure The primary outcome is any one of the following COVID-19 specific, inpatient, postoperative pulmonary complications (definitions are given in an Appendix in the protocol and through brief online training): • Pneumonia • Acute respiratory distress syndrome (ARDS) • Death
Definitions for each outcome are provided in the protocol. The components of the composite outcome have all been internationally validated. The feasibility of collecting these endpoints within routine care pathways has been demonstrated by our RECON cohort (11,500 patients, 4 countries).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 30 days following surgery |
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E.5.2 | Secondary end point(s) |
-Pneumonia -Acute respiratory distress syndrome (ARDS) -Death -Unexpected ventilation (unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation after surgery) -Postoperative diagnosis of COVID-19 infection based on microbiological testing or clinical features -Duration of hospital stay (including time spent in intensive care as well as ward level care) -Pulmonary function in keeping with the WHO Solidarity Trial outcome scale
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 30 days post surgery |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Control (normal practice) |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 100 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ghana |
India |
Nigeria |
South Africa |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial will be 12 months after the last data capture. This will allow sufficient time for the completion of protocol procedures, data collection, data input and analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |