Back to results

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

Primary Purpose

HIV Infections, Tuberculosis

Status

Completed

Phase

Phase 2

Locations

Thailand

Study Type

Interventional

Intervention

HAART containing nevirapine

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV-TB, nevirapine based HAART with rifampin treated TB, Compare PK profile, efficacy, safety and tolerability of HAART containing nevirapine 400mg/day versus 600 mg/day in HIV/TB co-infected patients, Treatment Naive

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Confirmed HIV positive after voluntary counseling and testing
Aged 18-60 years of age
Antiretroviral treatment naïve.
CD4+ cell count of < 200 cells/mm3 at the time of diagnosed TB
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.
No other active OI (CDC class C event)
Negative pregnancy test in females, and willing to use reliable contraception
Able to provide written informed consent.

Exclusion Criteria:

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.
Current use of steroid and other immunosuppressive agents.
Current use of any prohibited medications related to compliance and drug pharmacokinetics (see appendix )
Acute therapy for serious infection or other serious medical illness (in the judgment of the site Principal Investigator) requiring systemic treatment and/or hospitalization.
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.
The persons who had been received a mono-therapy of nevirapine
Unlikely to be able to remain in follow-up for the protocol defined period.
Patients with chronic active liver disease.
Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
Karnofsky performance score <30%

Sites / Locations

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
Chiangrai Hospital
Mae Chan Hospital
Phan Hospital
Bamrasnaradura Institute
Central Chest Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Arm Description

NVP 400 mg

NVP 600 mg

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Safety and tolerability of nevirapine based HAART 400 mg/day versus 600 mg/day

Nevirapine level at week 2, 4 and 12 and 12 hour PK at week 4 (only 20 patients)

Immune recovery syndrome, adherence, clinical improvement, incidence of new/recurrent AIDS events (CDC class C) between two group

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

Full Information

NCT ID

NCT00476853

First Posted

May 20, 2007

Last Updated

July 15, 2020

Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

other sponsors:Japanese MOPH, Labor and Welfare, Thai MOPH, Thai GPO, Bamrasnaradura Infectious Diseases Institute, Chiang Rai Hospital, King Chulalongkorn Memorial Hospital, Central General Chest Institute, The Research Institute of Tuberculosis (Japan)

1. Study Identification

Unique Protocol Identification Number

NCT00476853

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

October 2005 (undefined)

Primary Completion Date

September 2008 (Actual)

Study Completion Date

December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections, Tuberculosis

Keywords

HIV-TB, nevirapine based HAART with rifampin treated TB, Compare PK profile, efficacy, safety and tolerability of HAART containing nevirapine 400mg/day versus 600 mg/day in HIV/TB co-infected patients, Treatment Naive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

NVP 400 mg

Arm Title

Arm Type

Active Comparator

Arm Description

NVP 600 mg

Intervention Type

Drug

Intervention Name(s)

HAART containing nevirapine

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

Safety and tolerability of nevirapine based HAART 400 mg/day versus 600 mg/day

Time Frame

48 weeks

Title

Nevirapine level at week 2, 4 and 12 and 12 hour PK at week 4 (only 20 patients)

Time Frame

48 weeks

Title

Immune recovery syndrome, adherence, clinical improvement, incidence of new/recurrent AIDS events (CDC class C) between two group

Time Frame

48 weeks

Title

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

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Confirmed HIV positive after voluntary counseling and testing Aged 18-60 years of age Antiretroviral treatment naïve. CD4+ cell count of < 200 cells/mm3 at the time of diagnosed TB 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. No other active OI (CDC class C event) Negative pregnancy test in females, and willing to use reliable contraception Able to provide written informed consent. Exclusion Criteria: 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. Current use of steroid and other immunosuppressive agents. Current use of any prohibited medications related to compliance and drug pharmacokinetics (see appendix ) Acute therapy for serious infection or other serious medical illness (in the judgment of the site Principal Investigator) requiring systemic treatment and/or hospitalization. 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. The persons who had been received a mono-therapy of nevirapine Unlikely to be able to remain in follow-up for the protocol defined period. Patients with chronic active liver disease. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN. Karnofsky performance score <30%

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anchalee Avihingsanon, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Chiangrai Hospital

City

Chiang Rai

ZIP/Postal Code

57000

Country

Thailand

Facility Name

Mae Chan Hospital

City

Chiang Rai

ZIP/Postal Code

57000

Country

Thailand

Facility Name

Phan Hospital

City

Chiang Rai

ZIP/Postal Code

57000

Country

Thailand

Facility Name

Bamrasnaradura Institute

City

Nonthaburi

ZIP/Postal Code

11000

Country

Thailand

Facility Name

Central Chest Hospital

City

Nonthaburi

ZIP/Postal Code

11000

Country

Thailand

12. IPD Sharing Statement

Citations:

PubMed Identifier

18672531

Citation

Avihingsanon A, Manosuthi W, Kantipong P, Chuchotaworn C, Moolphate S, Sakornjun W, Gorowara M, Yamada N, Yanai H, Mitarai S, Ishikawa N, Cooper DA, Phanuphak P, Burger D, Ruxrungtham K. Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIV-tuberculosis coinfection receiving rifampicin. Antivir Ther. 2008;13(4):529-36.

Results Reference

derived

Links:

URL

http://www.hivnat.org

Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs