Efficacy and safety of Treamid in the rehabilitation of patients after COVID-19 pneumonia: a phase 2, randomized, double-blind, placebo-controlled trial

Abstract

Background: Many patients who recovered from COVID are still suffering from pulmonary dysfunction. Treamid (bisamide derivative of dicarboxylic acid, BDDA) was shown to have anti-inflammatory, and antifibrotic, effects in animal models of pulmonary fibrosis. This study was designed to assess the safety, tolerability, and efficacy of Treamid in the rehabilitation of patients after COVID pneumonia. The aim was to establish whether Treamid could be effective in ameliorating post-COVID sequelae.Methods: The phase 2, randomized, double-blind, placebo-controlled clinical trial was done at 8 medical centers in Russia. Patients with a diagnosis of COVID in the past medical history and having fibrotic changes in the lungs, decreased lung function, and moderate or severe dyspnea according to mMRC scale were enrolled and randomly assigned in a 1:1 ratio by use of interactive responsive technology to peroral administration of Treamid 50 mg or placebo once a day for 4 weeks. This trial was registered on ClinicalTrials.gov (Identifier: NCT04527354). The study was fully funded by PHARMENTERPRISES LLC.Results: 12 out of 29 patients (41%) in Treamid group achieved clinically significant improvement in FVC and/or DLCO compared to 5 out of 30 patients (17%) in placebo group (p = 0.036). There was a significant decrease of dyspnea according to modified Borg scale observed in the Treamid group (−0.9 ± 0.7 vs. −0.4 ± 0.8, p = 0.018). No significant differences in the adverse events were noted. Exploratory analysis of the female population indicated superiority of Treamid over placebo by decreasing dyspnea and the extent of lung damage as well as increasing TLC.Conclusions: Treamid was associated with clinically significant improvement in the post-COVID patients, evident by an increase in FVC and/or DLCO as well as decreasing dyspnea. Treamid was well tolerated and can be safely administered to patients discharged after COVID. Treamid was more effective in women visible by superior improvement of COVID sequalae after 4 weeks treatment. Considering that female gender is a risk factor associated with the development of post-COVID symptoms, Treamid might offer a pharmacological treatment for long-term sequalae after COVID and supports further investigation in future clinical trials in post-COVID patients.