Trial EudraCT 2020–001236–10
Publication Aman J, Lancet Respir Med, 2021 (published paper)
Dates: 2020-03-31 to 2021-01-04
Funding: Public/non profit (Amsterdam Medical Center Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ZonMW, and the European Union Innovative Medicines Initiative 2.)
Conflict of interest: Yes
Blinding: double blinding
Multicenter / Netherlands |
Follow-up duration (days): 28
|Inclusion criteria||Age >18 years ; Hospital admission with proven SARS2-Covid19 infection (confirmed with an RT-PCR test) ; Hypoxemic respiratory failure (SpO2 <94% or PaO2 <9kPa) ; Ability to give informed consent.|
|Exclusion criteria||Pre-existing chronic pulmonary disease, including: Known diagnosis of Interstitial Lung disease, Known diagnosis of COPD 4 or FEV1<30%pred, DLCO <45% (if test results are available), Total lung capacity (TLC) < 60% of predicted (if test results are available), Lung cancer with non-surgical treatment in last year ; Chronic home oxygen treatment ; Pre-existing heart failure with a known left ventricular ejection fraction <40% ; Active treatment of hematological or non-hematological cancer with targeted, immuno- or chemotherapy or thoracic radiotherapy in the last year ; Inability to provide informed consent ; Any subject who had received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study ; Active liver disease, porphyria or elevations of serums transaminases >5 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN ; History or suspicion of inability to cooperate adequately. ; White blood count < 4.0^109/l ; Hemoglobin < 6.0 mmol/l ; Thrombocytes < 100^109/l ; Pregnant female subjects (pregnancy test will be performed in all women of childbearing age prior to inclusion) ; Breastfeeding female subjects ; The use of strong Cyp3A4 inductors, including the following drugs: Carbamazepine, efavirenz, enzalutamide, fenobarbital, fenytoine, hypericum, mitotaan, nevirapine, primidon, rifabutine, rifampicine ; Concomittant use of chloroquine or hydroxychloroquine ; QTc >500msec at baseline.|
Initial dose: 800 mg orally on day 1 - Maintenance dose: 400 mg orally once a day on days 2-10.
400 participants (n1=204 / n2= 196)
|Characteristics of participants|
Mean age : 38.9
Severity : Mild: n=0 / Moderate: n=0/ Severe: n=385 Critical: n=0
|In the register|
Time to liberation from ventilation and supplemental oxygen >48h while being alive during a 28-day period after randomization (EudraCT)
|In the report|
Time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period after randomisation.
Yes. In English
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
In addition to the published article, the trial registry, protocol, statistical analysis plan, supplementary materials and replies from contact with authors were used in data extraction and assessment of risk of bias. The WHO scale for clinical improvement, reported in the article, was not included as an outcome measure in the registry or protocol, although the elements required to assign patients to points on the scale were included as secondary outcomes. There were no other substantive differences between the published article and the trial registry, protocol and statistical analysis plan in population, procedures, interventions or outcome measures. The study achieved its target sample size.
This study was updated on September 27th, 2021 with data gained from contact with authors.