Trial of High-Dose Rifampin in Patients With TB

Summary

The purpose of this study is to evaluate the potential of high doses of rifampin (RIF) to shorten treatment for tuberculosis (TB) without causing more adverse events. The hypotheses are that higher doses of RIF will result in higher blood concentrations of RIF; higher blood concentrations will result in tuberculosis bugs being killed more quickly; and, both of these will happen without more adverse events. Patients with active, infectious, drug-susceptible TB who agree to participate will be randomly assigned to 1 of 3 doses of RIF. All patients will also receive standard doses of regular (3) companion drugs for 2 months of daily, supervised therapy. The study will assess the following among the 3 study arms (oral doses of RIF 10, 15 \& 20 mg/kg/day) during the initial 8 weeks of treatment: 1) the amount of RIF in the blood after at least 14 days of treatment; 2) the difference in the number of tuberculosis bugs killed; 3) the frequency of adverse events.

Conditions

• Tuberculosis

Interventions

DRUG

Higher-Dose Rifampin

The intervention phase of this trial will last 8 weeks. During that time, subjects will receive the following companion drugs: isoniazid (INH, 5 mg/kg/day), ethambutol (EMB, 20 mg/kg/day), and pyrazinamide (PZA, 25 mg/kg/day), pyridoxine (50 mg), the standard doses used in treatment. Subjects will also be randomized to receive one of the following weight-based doses of the study drug, rifampin (RIF): 10 mg/kg/day (standard dose, control), 15 mg/kg/day (intervention 1), 20 mg/kg/day (intervention 2). All patients will receive at least standard dose of RIF, the efficacy of which in multidrug-treatment for TB is well established. Placebo will be used to control only the additional RIF capsules provided in the intervention arms.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• Sanofi

  collaborator INDUSTRY

• Harvard School of Public Health (HSPH)

  collaborator OTHER

• Brigham and Women's Hospital

  collaborator OTHER

• University of Liverpool

  collaborator OTHER

• St George's, University of London

  collaborator OTHER

• University of Florida

  collaborator OTHER

• Socios en Salud

  collaborator UNKNOWN

• Harvard University Faculty of Medicine

  lead OTHER

Principal Investigators

• Carole D Mitnick, Sc.D · Harvard Medical School (HMS and HSDM)

• Geraint Davies, B.M., Ph.D · University of Liverpool

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-09-30

Primary Completion

2016-04-30

Completion

2016-04-30

Countries

• United States
• Peru
• United Kingdom

Study Locations