A Randomized, Controlled, Phase III Clinical Trial to Evaluate the Efficacy and Tolerability of Risorine with Conventional Rifampicin in the Treatment of Newly Diagnosed Pulmonary Tuberculosis Patients.

BACKGROUND: The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity. To overcome these concerns a new boosted formulation of Rifampicin (Risorine) with bio-enhancer Piperine was developed. Piperine has been found to increase bioavailability of several drugs including Amoxicillin, Cefotaxime, Theophylline and Propranolol. Risorine is a fixed dose combination that contains Rifampicin 200 mg + Isoniazid 300 mg + Piperine 10 mg. AIM AND OBJECTIVE: The aim of the present study was to validate the therapeutic efficacy and tolerability of Risorine formulation containing regimen with a conventional regimen in the management of patients with newly diagnosed pulmonary tuberculosis. METHODS: Total 216 patients with sputum positive and treatment naïve pulmonary tuberculosis were enrolled in the study after fulfillment of inclusion / exclusion criteria. These patients were randomized to receive either a conventional anti-TB therapy (n = 117) or a similar regimen containing Risorine (n = 99) for 6 months. During the study period, symptomatic improvement, sputum conversion and radiological improvement were monitored at regular intervals. RESULTS: Of the 216 enrolled patients, 75% in the Risorine group and 79% in the control group completed the study. At 4 weeks the sputum conversion rate was significantly superior in Risorine group (93%) than the control group (84%), which was consistence throughout the study. Cure rate at the end of 24 weeks, was higher in Risorine group (92%) than in the control group (82%). Elevation of liver enzymes were observed in 3 patients in the Risorine group and in 9 patients in control group. CONCLUSIONS: Risorine, a novel formulation of low dose Rifampicin (200 mg), a bio enhancer Piperine (10 mg) and standard dose Isoniazid (300 mg) when given along with Ethambutol and Pyrazinamide was comparable in efficacy with standard WHO therapy using conventional formulation. Risorine provides more Rifampicin in blood compare to GI tract as well as maintaining higher blood levels on chronic therapy compared to conventional Rifampicin with better safety profile. Risorine gives higher sputum conversion rate during the Intensive Phase which is maintained till the end of study. Further a trend was also noticed towards better tolerability with newer formulation, Risorine. H = Isoniazid, R = Rifampicin, Z = Pyrazinamide and E = Ethambutol.