Trial NCT04365153
Publication Cremer P, The three C study, 2021 (published paper)
Dates: 4/28/2020 to 8/25/2020
Funding: Private (Novartis)
Conflict of interest: No
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / USA Follow-up duration (days): 150 | |
| Inclusion criteria | >= 18 years-old;
hospitalized for COVID-19 infection with a documented upper respiratory tract specimen positive for SARS-CoV2 RNA; had a troponin T >99th percentile upper reference range; NT-proBNP greater than the age-adjusted upper reference limit; C-reactive protein (CRP) >50 mg/L |
| Exclusion criteria | Alternative explanation for troponin elevation; Chronic Systolic Heart Failure with EF < 35%; Age < 18 years-old; Uncontrolled systemic bacterial or fungal infection; Concomitant viral infection (eg, Influenza or other respiratory virus); Pregnant; On mechanical circulatory support; On mechanical ventilation for greater than 48 hours; Resuscitated cardiac arrest; known hypersensitivity to canakinumab or any of its excipients; Neutrophil count <1000/mm3; history of myeloproliferative disorder or active malignancy receiving chemotherapy; known active tuberculosis or history of incompletely treated tuberculosis; Current treatment with immunosuppressive agents; Chronic prednisone use >10 mg/daily (for more than 3 weeks prior to admission); Has a history of solid-organ or bone marrow transplant; Severe preexisting liver disease with clinically significant portal hypertension; End-stage renal disease on chronic renal replacement therapy; Enrollment in another investigational study using immunosuppressive therapy; In the opinion of the investigator and clinical team, should not participate in the study; If male and sexually active, must have documented vasectomy or must practice birth control and not donate sperm during the study and for 3 months after study drug administration; Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug |
| Interventions | |
| Treatment 1 Canakinumab 600mg | |
| Control Placebo | |
| Control Canakinumab 300mg (* /* ) Co-Intervention: Standard care Duration : * | |
| Participants | |
| Randomized 45 participants n1=15/ n2=16/ n3=14 | |
| Characteristics of participants N=45 Mean age : NR 33 males Severity : Mild: n=4 / Moderate: n=20/ Severe: n=11 Critical: n=10 | |
| Primary outcome | |
| In the register Clinical Improvement at Day 14 [ Time Frame: Up to day 14 ] (Number of patients with either an improvement of two points on a seven category ordinal scale or discharge from the hospital) | |
| In the report Time to clinical improvement up to day 14, defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated No |
| 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 two published articles, the study registry (with outcome data posted online) and the protocol were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the population, intervention and control treatments, or in the primary outcomes. On 10th of August, 2021, this study was updated based on the published report in Eur Heart J. |