The IDEAL trial - a study protocol for a phase III randomized, double-blinded clinical trial assessing the ultra-short antibiotic prophylaxis of Isoniazid and Rifapentine in non-immunosuppressed patients with newly diagnosed latent tuberculosis

Abstract

Introduction

Tuberculosis (TB) is a global infectious disease that has plagued human beings for centuries. It currently ranks as one of the primary causes of death by a single agent. Treatment of latent TB (LTBI) is one of the cornerstones used to prevent the activation of TB. The current regimens are lengthy, associated with poor treatment adherence and several side effects. The need for shorter regimens is essential to control TB infection and accomplish the “End TB Strategy,” which has been proclaimed by the World Health Organization (WHO). Our study aims to provide a study design that assesses the efficacy of one month of Isoniazid (IHN) and Rifapentine (RFT) in non-immunosuppressed patients.

Methods

The proposed study will be a phase III, single-center, randomized, two-arms (1:1 ratio), double-blinded, placebo-controlled non-inferiority trial. We will include immunocompetent patients above the age of 18 with a new diagnosis of LTBI. Participants will be randomized, either receiving one month of INH with RFT or 6 months of INH alone with respective placebo to maintain blinding. The primary study outcome is the cumulative incidence of active TB in the studied treatment arms. The secondary outcome is the cumulative incidence and severity of adverse effects of the studied regimens.

Discussion

Given the scope and spread of LTBI around the globe, shorter and safer treatment options are of the utmost importance to eradicate TB. The proposed trial can contribute to this objective by improving the current standard of care. Potential disadvantages of the trial design include the need for many participants, trial duration, and costs.