Treatment shortening of drug-sensitive pulmonary tuberculosis using high-dose rifampicin for 3 months after culture conversion (Hi-DoRi-3): a study protocol for an open-label randomized clinical trial
Nakwon Kwak,
Doosoo Jeon,
Youngmok Park,
Young Ae Kang,
Kyung Jong Kim,
Young Ran Kim,
Byoung Soo Kwon,
Yong-Soo Kwon,
Hyung-Jun Kim,
Jae Ho Lee,
Ji Yeon Lee,
Jung-Kyu Lee,
Jeongha Mok,
Minkyoung Cheon,
Jiwon Park,
Seokyung Hahn,
Jae-Joon Yim
Affiliations
Nakwon Kwak
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine
Doosoo Jeon
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital
Youngmok Park
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital
Young Ae Kang
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital
Kyung Jong Kim
Department of R&D, Korean Institute of Tuberculosis
Young Ran Kim
Clinical Research Section, International Tuberculosis Research Center
Byoung Soo Kwon
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital
Yong-Soo Kwon
Department of Internal Medicine, Chonnam National University Medical School, Chonnam National University Hospital
Hyung-Jun Kim
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital
Jae Ho Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital
Ji Yeon Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Center
Jung-Kyu Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Boramae Medical Center
Jeongha Mok
Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Hospital
Minkyoung Cheon
Medical Research Collaborating Center, Seoul National University Hospital
Jiwon Park
Medical Research Collaborating Center, Seoul National University Hospital
Seokyung Hahn
Medical Research Collaborating Center, Seoul National University Hospital
Jae-Joon Yim
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine
Abstract Background The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted. Methods This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited. Discussion This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB. Trial registration ClinicalTrials.gov NCT04485156 . Registered on July 24, 2020.
