A Randomized Single Blind Controlled Trial of Combination Therapy (Spironolactone and Sitagliptin) in Hospitalized Adult Patients with Covid-19

Background: COVID-19 may cause respiratory distress syndrome, ICU admission and death. Treatment of COVID-19 to prevent hospitalization, respiratory distress syndrome and death remains a priority. Our investigation sought to determine whether combination of spironolactone and Sitagliptin could reduce hospitalization for outpatient and death for inpatient with SARS-CoV-2 infection. Methods: This single blind, 4-arms, prospective randomized clinical trial was conducted at Shiraz University of Medical Sciences and Bushehr University of Medical Sciences hospitals during the second wave of the COVID-19 pandemic between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into four groups: control (standard therapy), combination (Sitagliptin, spironolactone and standard therapy), Sitagliptin (Sitagliptin and standard therapy) or spironolactone (spironolactone and standard therapy). The primary outcome was the clinical improvement of the patients in the hospital as measured on an eight-point numerical scale ranging from no limitation of activities (score 1) to death (score 8). The secondary outcomes included intubation, ICU admission, end organ damages, CT findings and paraclinical information. We also treated 60 outpatients with SARS-CoV-2 infection to assess hospitalization rate. Results: 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), Sitagliptin group (66 patients) and Spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes. However, the mortality rate was lower in spironolactone receivers. Our intervention reduced lung infiltration but not the area of involvement in lung. The combination (Sitagliptin, spironolactone) therapy for outpatients with SARS-CoV-2 infection could reduce hospitalization rate to less than 2 percent. Conclusion: Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients. Furthermore, early prescription of this combination can reduce hospitalization rate. Clinical Trial Registration Details: IRCT registration number: IRCT20201003048904N2, Registration date: December 10, 2020. Funding Information: This project is supported by Shiraz University of Medical Sciences, Bushehr University Medical Sciences, Faghihi Hospital and Shohadaye_Khalije_Fars Hospital. Declaration of Interests: The author has declared that no conflict of interest exists. Ethics Approval Statement: The ethics committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1399.550) and Bushehr University of Medical Sciences (IR.BPUMS.REC.1399.140) approved the study. We followed the declaration of Helsinki and Iranian national guidelines for ethics in research to design the study. The research physicians had routinely collected a written formal informed consent at the time of admission.