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The Pharmacokinetics and Safety of IDV/r With NRTIs in HIV/TB Co-infected Patients Receiving Rifampicin

Primary Purpose

HIV Infections, Tuberculosis

Status
Completed
Phase
Phase 1
Locations
Thailand
Study Type
Interventional
Intervention
indinavir/ritonavir
Sponsored by
The HIV Netherlands Australia Thailand Research Collaboration
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring indinavir/ritonavir, HIV/TB, rifampicin, PK and efficacy of IDV/RTV 600/100 mg BID with rifampicin, Treatment Naive

Eligibility Criteria

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

Inclusion Criteria:

  • Confirmed HIV positive after voluntary counselling and testing
  • Aged between 18 and 60 years of age
  • Antiretroviral treatment naive
  • CD4+ cell count of <200 cells/mm3 at the time of TB diagnosis
  • ALT <5 times ULN
  • Serum creatinine <1.4 mg/dl
  • Haemoglobin >8 mg/L
  • TB diagnosis; either probable (clinical symptoms plus chest x-ray and response to anti-TB medication) or definitive( sputum AFB culture confirmed) and receiving or planning to receive rifampicin-containing anti-TB therapy for at least a 2 week period before the initiation of ART
  • No other active OI (CDC class C event)
  • Able to provide written informed consent

Exclusion Criteria:

  • Current use of steroids and other immunosuppressive agents
  • Current use of any prohibited medications related to compliance and drug pharmacokinetics
  • 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.
  • Previous exposure to nevirapine monotherapy
  • Unlikely to be able to remain in follow-up for the protocol defined period
  • 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

  • HIV-NAT Thai Red Cross AIDS Research Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

1

Arm Description

IDV/r 600/100 mg + rifampicin

Outcomes

Primary Outcome Measures

pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy.

Secondary Outcome Measures

safety of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy
efficacy of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy
the prevalence of immune recovery syndrome of TB and other HIV-related conditions after ritonavir-boosted indinavir 600/100mg bid

Full Information

First Posted
December 14, 2006
Last Updated
July 15, 2020
Sponsor
The HIV Netherlands Australia Thailand Research Collaboration
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1. Study Identification

Unique Protocol Identification Number
NCT00411996
Brief Title
The Pharmacokinetics and Safety of IDV/r With NRTIs in HIV/TB Co-infected Patients Receiving Rifampicin
Official Title
The Pharmacokinetics and Safety of Ritonavir-boosted Indinavir 600/100mg Bid Combined With NRTIs in ARV naïve HIV/TB Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
October 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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
We believe that there is a strong rationale for the study of IDV/r 600/100 bid as a boosted-PI combination that, in the presence of RMP, is able to produce a satisfactory PK profile associated with adequate antiretroviral potency, tolerability and efficacy.
Detailed Description
The fixed-dose combination of d4T+3TC+NVP (GPOvir) has been widely used in Thailand since June 2002. The prevalence of NNRTI resistance has increased since 2005. Efavirenz-based antiretroviral therapy (ART) is preferred in patients with TB/HIV receiving rifampin-containing TB regimens. However, efavirenz cannot be used in the context of NNRTI failure, intolerance or toxicity. The optimal ART in populations receiving rifampicin remains unknown. Rifabutin, which is recommended in combination with a boosted protease inhibitor (PI/r) is expensive and not available in Thailand and other developing countries. Ritonavir-boosted indinavir (IDV/r) is potent and the cheapest boosted PI available in Thailand. If IDV/r in combination with rifampin demonstrates suitable pharmacokinetics and is well tolerated, this regimen might prove useful and could be widely implemented. However, high rates of gastrointestinal and renal toxicity have been demonstrated in Thai patients receiving standard doses of IDV/r 800/100 BID. We believe that there is a strong rationale to study if IDV/r 600/100 BID in combination with rifampin is able to produce a satisfactory pharmacokinetic profile, with antiretroviral potency, tolerability and efficacy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Tuberculosis
Keywords
indinavir/ritonavir, HIV/TB, rifampicin, PK and efficacy of IDV/RTV 600/100 mg BID with rifampicin, Treatment Naive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Other
Arm Description
IDV/r 600/100 mg + rifampicin
Intervention Type
Drug
Intervention Name(s)
indinavir/ritonavir
Intervention Description
IDV/r 600/100 mg BID + rifampicin OD for at least 2 weeks
Primary Outcome Measure Information:
Title
pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy.
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
safety of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy
Time Frame
48 weeks
Title
efficacy of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy
Time Frame
48 weeks
Title
the prevalence of immune recovery syndrome of TB and other HIV-related conditions after ritonavir-boosted indinavir 600/100mg bid
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
No
Eligibility Criteria
Inclusion Criteria: Confirmed HIV positive after voluntary counselling and testing Aged between 18 and 60 years of age Antiretroviral treatment naive CD4+ cell count of <200 cells/mm3 at the time of TB diagnosis ALT <5 times ULN Serum creatinine <1.4 mg/dl Haemoglobin >8 mg/L TB diagnosis; either probable (clinical symptoms plus chest x-ray and response to anti-TB medication) or definitive( sputum AFB culture confirmed) and receiving or planning to receive rifampicin-containing anti-TB therapy for at least a 2 week period before the initiation of ART No other active OI (CDC class C event) Able to provide written informed consent Exclusion Criteria: Current use of steroids and other immunosuppressive agents Current use of any prohibited medications related to compliance and drug pharmacokinetics 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. Previous exposure to nevirapine monotherapy Unlikely to be able to remain in follow-up for the protocol defined period 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
Kiat Ruxrungtham, MD
Organizational Affiliation
HIV-NAT, Thai Red Cross AIDS Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
HIV-NAT Thai Red Cross AIDS Research Center
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
22250979
Citation
Avihingsanon A, van der Lugt J, Singphore U, Gorowara M, Boyd M, Ananworanich J, Phanuphak P, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of adjusted dose indinavir/ritonavir in rifampicin-treated HIV/tuberculosis-coinfected patients: a pilot study. AIDS Res Hum Retroviruses. 2012 Oct;28(10):1170-6. doi: 10.1089/AID.2011.0247. Epub 2012 Mar 6.
Results Reference
derived
Links:
URL
http://www.hivnat.org
Description
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Learn more about this trial

The Pharmacokinetics and Safety of IDV/r With NRTIs in HIV/TB Co-infected Patients Receiving Rifampicin

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