Efficacy Safety Study Comparing 2 Doses of NVP After Initiating Rifampin-containing TB Therapy

HIV Infections Clinical Trial

Official title:

A 48 Week, Randomized, Open-label, 2 Arm Study to Compare the Efficacy, Safety and Tolerability of HAART Containing Nevirapine 400mg/Day Versus Nevirapine 600 mg/Day in HIV-1 Infected Patients Started at 2-6 Weeks After Initiating Rifampin Containing Antituberculous Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00476853
• Other study ID #: HIV-NAT 033
• Status: Completed
• Phase: Phase 2
• Start date: October 2005
• Est. completion date: December 2009

Study information

• Verified date: July 2020
• Source: The HIV Netherlands Australia Thailand Research Collaboration
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A 48 week, randomized, open-label, two arm study to compare the efficacy, safety and tolerability of HAART containing nevirapine 400 mg/day versus nevirapine 600 mg/day in HIV-1 infected patients started at 2-6 weeks after initiating rifampicin containing antituberculosis therapy.

Description:

Preliminary data from the HIVNAT PK laboratory indicate that out of 5/60 patients treated with nevirapine (200 mg bid) and rifampicin had sub-therapeutic nevirapine levels (<3.0 mg mg/L). In a control group of 38 patients using nevirapine without rifampicin there were no sub-therapeutic levels. A dose increase of nevirapine while patients who are receiving that rifampicin may be required. Both nevirapine and rifampicin are tepatotoxic agents as are other agents used in treatment of HIV or tuberculosis. Using a higher nevirapine may prevent the occurrence of sub-therapeutic nevirapine levels, but may also induce more liver toxicity. To address these issues, we designed a randomized prospective study to evaluate the safety, efficacy and pharmacokinetics of nevirapine 400 mg/day versus 600 mg/day with a two weeks lead-in 200 mg/day and 400 mg/day respectively, in TB-HIV co-infected patients who taking rifampicin and short-term efficacy and toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: December 2009
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Confirmed HIV positive after voluntary counseling and testing

2. Aged 18-60 years of age

3. Antiretroviral treatment naïve.

4. CD4+ cell count of < 200 cells/mm3 at the time of diagnosed TB

5. TB is diagnosed and using treatment with rifampin base therapy for at least 2 weeks but no longer than 4 weeks duration. The requirement for study entry is at least one acid-fast bacillus (AFB) positive smear with a typical syndrome and/or CXR findings consistent with pulmonary TB. Pulmonary TB and / or extra pulmonary TB will be included if AFB or culture for TB is positive.

6. No other active OI (CDC class C event)

7. Negative pregnancy test in females, and willing to use reliable contraception

8. Able to provide written informed consent.

Exclusion Criteria:

1. The following laboratory variables, i. absolute neutrophil count (ANC) < 1000 cells/uL ii. hemoglobin < 6.5 g/dL iii. platelet count < 50,000 cells/uL iv. serum AST, ALT > 5 x ULN vi. serum bilirubin > 2 x ULN vii. serum creatinine > 2 x ULN viii. Pregnant or nursing mothers.

2. Current use of steroid and other immunosuppressive agents.

3. Current use of any prohibited medications related to compliance and drug pharmacokinetics (see appendix )

4. Acute therapy for serious infection or other serious medical illness (in the judgment of the site Principal Investigator) requiring systemic treatment and/or hospitalization.

5. Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.

6. The persons who had been received a mono-therapy of nevirapine

7. Unlikely to be able to remain in follow-up for the protocol defined period.

8. Patients with chronic active liver disease.

9. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.

10. Karnofsky performance score <30%

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• HAART containing nevirapine
Initially NVP 200 mg BID (400 mg per day) was compared to 400 mg BID and 200 mg OD NVP (600 mg per day). 400 mg/day versus 600 mg/day.

Locations

Country	Name	City	State
Thailand	The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)	Bangkok
Thailand	Chiangrai Hospital	Chiang Rai
Thailand	Mae Chan Hospital	Chiang Rai
Thailand	Phan Hospital	Chiang Rai
Thailand	Bamrasnaradura Institute	Nonthaburi
Thailand	Central Chest Hospital	Nonthaburi

Sponsors (10)

Lead Sponsor	Collaborator
The HIV Netherlands Australia Thailand Research Collaboration	Bamrasnaradura Infectious Diseases Institute, Central General Chest Institute, Chiang Rai Hospital, King Chulalongkorn Memorial Hospital, Labor and Welfare, other sponsors:Japanese MOPH, Thai GPO, Thai MOPH, The Research Institute of Tuberculosis (Japan)

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of nevirapine based HAART 400 mg/day versus 600 mg/day on HIV-1 load as measured by HIV-1 RNA quantification in plasma		48 weeks
Secondary	Safety and tolerability of nevirapine based HAART 400 mg/day versus 600 mg/day		48 weeks
Secondary	Nevirapine level at week 2, 4 and 12 and 12 hour PK at week 4 (only 20 patients)		48 weeks
Secondary	Immune recovery syndrome, adherence, clinical improvement, incidence of new/recurrent AIDS events (CDC class C) between two group		48 weeks
Secondary	Time to mortality or new/recurrent AIDS events (CDC class C), 1 year mortality rate of TB/HIV patients, emerging of ARV resistant especially nevirapine, emerging of anti-TB resistance		48 weeks

External Links

•   The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)