Phase 2
N=180
Trial of High-Dose Rifampin in Patients With TB
Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT01408914 ↗Enrolled (actual)
180
Serious AEs
4.4%
Results posted
Jul 2017
Primary outcome: Primary: Steady State Pharmacokinetic Exposure of RIF — 115.6988; 201.9725; 284.4278 Ratio
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Higher-Dose Rifampin (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Harvard University Faculty of Medicine
- Primary completion
- Apr 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Steady State Pharmacokinetic Exposure of RIF |
115.6988; 201.9725; 284.4278 | — |
| SECONDARY Sputum Culture Sterilization During the Initial 8 Weeks of Treatment |
46; 44; 45 | — |
| SECONDARY Incidence of Rifampin-related Grade 2 or Higher Adverse Events |
26; 31; 23 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Newly diagnosed pulmonary TB with acid-fast bacilli (>=2+) in a stained sputum smear, ultimately confirmed by culture.
- Susceptibility of isolate to INH and RIF by HAIN test.
- Willingness to undergo HIV testing according to the National Health Guidelines for TB control in Peru. The study will also consider patients who have had negative HIV serostatus documented within six months prior to enrollment or if verifiable positive serostatus was documented using a validated test any time previously.
- Age >/= 18 years and 7.5%).
- Refusal to be tested for HIV infection; HIV infection with contraindication for treatment with efavirenz (including resistance).
- Pulmonary silicosis.
- Breastfeeding.
- Rifampin contraindications such as hypersensitivity or jaundice.
- Likely difficulty adhering to the protocol, as assessed by the investigator.
- Laboratory results in the 14 days preceding enrollment showing:
- Serum amino alanine transferase (ALT) >2 times upper limit of normal
- Serum total bilirubin concentration >2.5 times upper limit of normal
- Serum creatinine concentration > 2 times upper limit of normal and/or creatinine clearance <60 mL/min
- Hemoglobin concentration < 7.0 g/dL
- Platelet count < 150,000/mm3
- White blood count <4500 cells/μL.
- Having a serological test positive for HBVsAg (hepatitis B virus surface antigen) or for HCVAb (hepatitis C virus antibody)test.
Data sourced from ClinicalTrials.gov (NCT01408914). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.