Trial ISRCTN40580903, EudraCT 2020-001684-85
Publication Fisher B, CATALYST, 2021 (preprint)
Dates: 6/15/2020 to 2/18/2021
Funding: Public/non profit (Medical Research Council)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / UK Follow-up duration (days): 28 | |
| Inclusion criteria | 16 years or over; clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription-polymerase chain reaction (RT-PCR) assay); C-Reactive Protein (CRP) ⥠40 mg/L. The requirement for raised CRP replaced an inclusion criterion for low oxygenation status (oxygen saturation â¤94% while breathing ambient air or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen â¤300 mmHg) early in the course of recruitment following a change in primary outcome. |
| Exclusion criteria | Planned palliative care; pregnancy or breastfeeding; women of childbearing potential and non-vasectomised men who were unwilling to use effective contraception for the duration of the trial and throughout the drug-defined post-trial period; known HIV or chronic hepatitis B or C infection; concurrent immunosuppression with biological agents; a history of haematopoietic stem cell or solid organ transplant; known hypersensitivity to drug products or excipients; tuberculosis or other severe infections such as (nonSARS-CoV-2) sepsis, abscesses, and opportunistic infections requiring treatment; moderate or severe heart failure (NYHA class III/IV); any other indication or medical history, that in the opinion of the patientâs local investigator, made the patient unsuitable for trial participation |
| Interventions | |
| Treatment 1 Namilumab | |
| Control Standard care | |
| Treatment 3 Infliximab | |
| Participants | |
| Randomized 146 participants n1=57/ n2=54n3=35 | |
| Characteristics of participants N=146 Mean age : NR 90 males Severity : Mild: n=0 / Moderate: n=*/ Severe: n=* Critical: n=* | |
| Primary outcome | |
| In the register The ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2). | |
| In the report CRP, collected over time until day 14. (originally th eprimary outcome was the ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2), later (before any analysis of trial data) changed to CRP due to modelling of data from a large cohort of patients hospitalised in the first wave, indicated that the SF ratio might not be a viable outcome measure of sickness) | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated NR |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the pre-print article with supplementary appendices, the prospective study registries (ISRCTN 2020-05-14, EudraCT 2020-04-17) and protocol were used in data extraction and risk of bias assessment. In this adaptive platform trial, the infliximab arm was stopped in January 2021 due to futility. In February 2021 the namilumab arm was also stopped due to recent changes to standard of care with routine use of tocilizumab. As a result, the trial (n = 146) did not achieve its target sample size (n = 168). The original primary outcome, oxygen saturation to fraction of inspired oxygen ratio, was changed to C-reactive protein before data analysis due to subsequent modelling of data from a large cohort of patients hospitalised in the first wave indicated that the SF ratio might not be a viable outcome measure of sickness. There is no change from the trial registrations or protocol in the intervention and control treatments. |