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

July 15, 2020 updated by: The HIV Netherlands Australia Thailand Research Collaboration

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Bangkok, Thailand, 10330
        • HIV-NAT Thai Red Cross AIDS Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 1
IDV/r 600/100 mg + rifampicin
Drug: indinavir/ritonavir
IDV/r 600/100 mg BID + rifampicin OD for at least 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy.
Time Frame: 2 weeks
2 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
safety of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy
Time Frame: 48 weeks
48 weeks
efficacy of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy
Time Frame: 48 weeks
48 weeks
the prevalence of immune recovery syndrome of TB and other HIV-related conditions after ritonavir-boosted indinavir 600/100mg bid
Time Frame: 48 weeks
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Investigators

  • Principal Investigator: Kiat Ruxrungtham, MD, HIV-NAT, Thai Red Cross AIDS Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

December 14, 2006

First Submitted That Met QC Criteria

December 14, 2006

First Posted (Estimate)

December 15, 2006

Study Record Updates

Last Update Posted (Actual)

July 17, 2020

Last Update Submitted That Met QC Criteria

July 15, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HIV-NAT 044

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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