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

This study has been completed.
Sponsor:
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT00411996
First received: December 14, 2006
Last updated: June 4, 2010
Last verified: June 2010

December 14, 2006
June 4, 2010
December 2006
October 2008   (final data collection date for primary outcome measure)
pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy. [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy.
Complete list of historical versions of study NCT00411996 on ClinicalTrials.gov Archive Site
  • safety of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • efficacy of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • the prevalence of immune recovery syndrome of TB and other HIV-related conditions after ritonavir-boosted indinavir 600/100mg bid [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • 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
Not Provided
Not Provided
 
The Pharmacokinetics and Safety of IDV/r With NRTIs in HIV/TB Co-infected Patients Receiving Rifampicin
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Tuberculosis
Drug: indinavir/ritonavir
IDV/r 600/100 mg BID + rifampicin OD for at least 2 weeks
Active Comparator: 1
IDV/r 600/100 mg + rifampicin
Intervention: Drug: indinavir/ritonavir
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. Epub 2012 Mar 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
December 2009
October 2008   (final data collection date for primary outcome measure)

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%
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT00411996
HIV-NAT 044
Yes
Kiat Ruxrungtham, HIV-NAT
The HIV Netherlands Australia Thailand Research Collaboration
Not Provided
Principal Investigator: Kiat Ruxrungtham, MD HIV-NAT, Thai Red Cross AIDS Research Center
The HIV Netherlands Australia Thailand Research Collaboration
June 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP