Efficacy and safety of Chinese medicine compound for the convalescent COVID-19 patients: Protocol of a multi-centered, randomized, double-blinded, placebo-controlled clinical trial (Preprint)

UNSTRUCTURED ABSTRACT Background: Convalescent coronavirus disease 2019 (COVID-19) refers to a series of clinical syndromes in patients with COVID-19 infection that follow the relevant discharge indications but do not fulfill the criteria for a clinical cure, and these patients are discharged from the hospital with residual multifunctional deficits, including coughing, fatigue, and insomnia. Due to the prolonged convalescent COVID-19 infection, patients continue to experience symptoms or develop new symptoms after three months of infection, and some symptoms persist for over two months without any apparent triggers, which has a significant impact on the health status and quality of life of the population. Patients with convalescent COVID-19 lack a definitive pharmacological treatment. Traditional Chinese medicine (TCM) exhibits a distinct, synergistic effect on the treatment of convalescent COVID-19. However, there exists a limited number of clinical trials on TCM with lower evidence levels in convalescent COVID-19; therefore, randomized trials are urgently required. Methods: A multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial was performed to evaluate the efficacy and safety of Shenlingkangfu (SLKF) granules in treating patients with convalescent COVID-19 and lung-spleen qi deficiency syndrome. Eligible participants were aged 18–75 years, had a confirmed or physician-suspected severe acute respiratory syndrome coronavirus 2 infection at least six months prior, and satisfied clinical criteria. Individuals with a history of severe pulmonary dysfunction or major liver and kidney illness or those on medications were excluded. Multicenter subjects satisfying all criteria were assigned (1:1) randomly into an intervention group and a control group. After a 2-day adjustment period, A total of 154 participants were randomly divided into an intervention group and a control group. The intervention group was given the SLKF granules orally once a bag, 16.9 g, twice daily, whereas the control group received the SLKF granule simulation at the same dosage. The trial was conducted over 14 days, with assessments performed at baseline and 14 days. Results: The primary outcomes were the therapeutic efficacy rate and total clinical symptom score. The secondary outcomes included the fatigue self-assessment scale, pain visual analog scale, Pittsburgh sleep quality index, mini-mental state examination, hospital anxiety and depression scale, TCM syndrome score, C-reactive protein, erythrocyte sedimentation rate, and interleukin-6. Three routine examinations, liver and kidney function tests, and electrocardiography were used as safety indicators. Conclusions:This study aimed to verify whether SLKF granules can significantly improve clinical symptoms, including fatigue, loss of appetite, cough, phlegm, and insomnia, in patients with convalescent COVID-19. For a comprehensive investigation, additional clinical trials with larger sample sizes and longer intervention periods are required.Clinical Trial Registration Center NCT1900024524, Registered on 26 January, 2024.