Trial NCT04365127
Publication Ghandehari S, SSRN, 2020 (preprint)
Dates: 2020-04-27 to 2020-08-20
Funding: Private (The Institut Biochimique SA (IBSA, Lugano, Switzerland))
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Single center / USA Follow-up duration (days): 15 | |
| Inclusion criteria | 1. Hospitalized adult (≥18 years old) genetic male patients with
2. Laboratory-confirmed COVID-19 as determined by PCR, or other commercial or public health assay, as documented by either of the following: a. in any specimen < 72 hours prior to randomization; b. in any specimen collected ≥ 72 hours prior to randomization, with progressive disease suggestive of ongoing COVID-19 infection. 3. Patient (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. 4. Patient understands and agrees to comply with planned study procedures. 5. Patient agrees to the collection of venous blood per protocol. 6. Illness of any duration and at least one of the following: Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air and/or requiring supplemental oxygen at no more than FiO2 50% by high flow nasal cannula. 7. Patient must agree to be placed on anticoagulation for prevention of deep venous thrombosis (DVT) while hospitalized. 8. Patient must agree to use suitable barrier method of contraception for the duration of the study. |
| Exclusion criteria | 1. ALT/AST >5 times the upper limit of normal. 2. History of thromboembolic disease. 3. History of breast cancer. 4. Allergy to progesterone or betacyclodextrin. 5. History of seizure disorder. 6. Use of supplemental oxygen prior to hospital admission. 7. Requiring higher than 50% supplemental oxygen by high flow nasal cannula or mechanical ventilation. 8. Enrolment in any other interventional clinical trials for COVID-19. |
| Interventions | |
| Treatment
Progesterone 100 mg subcutaneously twice a day for up to 5 days. |
|
| Control
Standard care Definition of Standard care: institutional standard of care (SOC) | |
| Participants | |
| Randomized 42 participants (n1=20 / n2= 22) | |
| Characteristics of participants N=42 Mean age : 55.3 40 males Severity : Mild: n=6 / Moderate: n=31/ Severe: n=3 Critical: n=0 | |
| Primary outcome | |
| In the register Change in clinical status of subjects at Day 7 based on the following 7-point ordinal scale: a. Death; b. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); c. Hospitalized, on high flow oxy | |
| In the report Change in clinical status of participants from baseline to Day 7 | |
| Documents available |
Protocol NR Statistical plan NR 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, the trial registry was used in data extraction and assessment of risk of bias. Neither study protocol not statistical analysis plan was available. The study achieved its pre-stated sample size. There were no substantive differences in population or procedures between the pre-print article and the trial registry. The time-point for the primary outcome was changed in the registry after completion of recruitment and follow up. Adverse events and serious adverse events were not pre-specified in the registry. The study only reported a list of non-serious Grade 3 and 4 adverse events which could not be extracted for Total adverse events as it does not account for Grades 1 and 2.
According to the Procedures section of the report, "control patients with significant clinical deterioration, requiring higher supplemental oxygen through high flow devices or mechanical ventilation at any point during the study, or those at Day 7 without clinical improvement were permitted to cross over to receive progesterone therapy." Furthermore, change in clinical status of subjects on day 15 was registered as an outcome but not reported as such in the paper/report. Only death at day 15 was able to be determined from the Results text of the paper/report. |