This study was a randomized clinical trial that was performed from April 2020 until August 2020 in Khorshid hospital affiliated with Isfahan University of Medical Sciences. This study was conducted on 60 severe Covid-19 hospitalized patients. The study protocol was approved by Research Committee of Isfahan University of Medical Sciences and the Ethics Committee has confirmed it (IR.MUI.MED.REC.1399.027). Iranian registry for clinical trial code is IRCT20170207032444N3
Hospitalized patients were eligible for the trial if clinical symptoms and signs were compatible with Covid-19 infection and positive PCR test or lung HRCT abnormalities compatible with Covid-19 pneumonia, they were 18-75-year-old men and 50-75-year-old women admitted in hospital and had these criteria, SpO2 less than 85% at admission, no need to intubation in first 24 hours of admission and no multiorgan failure or shock state at presentation
All the patients or their legal representatives, if they were not able to provide consent, signed the informed consent.
Patients were excluded if they had hepatic failure (Child Pugh score ≥ C, AST > 5 times of the upper limit normal) or severe renal dysfunction (glomerular filtration rate (GFR) less than 30 CC per min).
Sixty patients were selected based on inclusion criteria. We collected demographic data of all patients including age, gender, the time interval between symptom onset and admission, smoking status, and comorbidities. The mean O2 saturation by the time of admission was also noted. Patients were randomly assigned in 1:1 ratio to 2 groups each containing 30 patients. Randomization was done through random sequence generation by using statistical software. The first group received thalidomide and the other group received the usual care for Covid-19 infection.
Patients in both groups received methylprednisolone 50 mg intravenously every 12 hours for 3 days and then daily for 7 days, hydroxychloroquine 200 mg orally every 12 hours for 5 days.
For symptom control (pain, cough, nausea, and vomiting) acetaminophen codeine, diphenhydramine, dimenhydrinate, and promethazine were prescribed. Antibiotics were administered based on physician choice (Ceftriaxone, Azithromycin, and Vancomycin). All patients received enoxaparin 40 mg subcutaneously daily during hospitalization.
Patients in the intervention group received thalidomide tablets (Talidex, Alan pharmaceuticals) 100 mg daily for 14 days added to the usual treatment.
All patients were visited daily by an Internist or Pulmonologist and were followed weekly for 4 weeks using phone calls. During follow up adherence to prescribed thalidomide was monitored by a specialized nurse.
ICU admission rate of patients in both groups was assessed as the primary outcome. Rate of intubation and mortality were also evaluated and compared between two groups as the secondary outcomes.
We also evaluated adverse effects related to thalidomide. These adverse effects included peripheral neuropathy, somnolence, constipation, skin rash, neutropenia, weakness, orthostatic hypotension, headache, and peripheral edema (18).
Data were collected and analyzed using SPSS software version 21. Continuous and categorical variables were reported as mean ± Standard deviation (SD) and frequency (percentage) and compared with independent samples t-test and Chi-squared test, respectively. Kaplan-Meir and log-rank test used for comparing the study outcomes (as the time to event data) and results were reported as hazard ratio and 95% confidence interval (95%CI). P-value < 0.05 was considered as the significance level.