Status:
COMPLETED
Trial of High-Dose Rifampin in Patients With TB
Lead Sponsor:
Harvard University Faculty of Medicine
Collaborating Sponsors:
National Institute of Allergy and Infectious Diseases (NIAID)
Sanofi
Conditions:
Tuberculosis
Eligibility:
All Genders
18-60 years
Phase:
PHASE2
Brief 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 do...
Detailed Description
This is a Phase II, multi-site, dose-ranging trial comparing 3 doses of RIF in a multidrug regimen for treatment of smear-positive, pulmonary TB. The intervention phase of this prospective, randomized...
Eligibility Criteria
Inclusion
- 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 \<61 years.
- Signed informed consent.
- Negative serum pregnancy test (women of childbearing potential).
- Women with child-bearing potential must agree to practice a double-barrier method of birth control during treatment. Adequate contraceptives (condoms and spermicide) will be provided by the study to avoid pregnancy among female subjects.
- Karnofsky score of at least 50 (requires considerable assistance and frequent medical care).
- Intends to remain in jurisdiction of health center during study and follow up.
Exclusion
- Body weight \<30 kg.
- Prior treatment with multidrug anti-TB therapy for more than one month.
- Resistance on HAIN to INH and/or RIF. These patients will be treated according to local programmatic guidelines.
- Central nervous system or miliary TB.
- Clinical or radiological signs suggestive of pericardial or pleural involvement.
- Presence of significant hemoptysis. Patients who cough up frank blood (more than blood-streaked sputum) will not be eligible for enrollment.
- Known intolerance to any of the study drugs; use of concomitant drugs that interfere with the pharmacokinetics of anti-TB drugs; use of concomitant hepatotoxic drugs (other than companion study drugs) for which potential drug interactions or synergistic toxicity are known: boosted protease inhibitors, non-nucleoside reverse transcriptase inhibitors, azole antifungals and statins; use of antibiotics that are contraindicated during the study's TB therapy; current daily use of acetaminophen or paracetamol for two weeks or more.
- History of liver disease.
- Uncontrolled condition that might interfere with drug absorption, distribution, metabolism or excretion (i.e. chronic gastrointestinal disease, renal insufficiency defined by creatinine clearance \<60mL/min).
- Uncontrolled diabetes mellitus (HbA1c\>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.
Key Trial Info
Start Date :
September 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 1 2016
Estimated Enrollment :
180 Patients enrolled
Trial Details
Trial ID
NCT01408914
Start Date
September 1 2013
End Date
April 1 2016
Last Update
November 20 2017
Active Locations (4)
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1
University of Florida
Gainesville, Florida, United States, 32610-0486
2
Socios En Salud Sucursal Perú
Lima, Peru
3
School of Clinical Sciences at University of Liverpool
Liverpool, United Kingdom
4
St. George's University of London
London, United Kingdom