Pharmacokinetics (PK) and Safety of 2 Different Doses of Lopinavir/Ritonavir in in HIV/Tuberculosis (TB) Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Department of Disease Control, Ministry of Public Health Thailand
Information provided by (Responsible Party):
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT01138202
First received: June 4, 2010
Last updated: March 27, 2015
Last verified: March 2015

June 4, 2010
March 27, 2015
November 2010
December 2015   (final data collection date for primary outcome measure)
plasma concentration level [ Time Frame: 12 hours ] [ Designated as safety issue: Yes ]
Percentage of plasma concentration level above an acceptable lower limit (lopinavir Cmin > 1 mg/L) at steady-state.
Same as current
Complete list of historical versions of study NCT01138202 on ClinicalTrials.gov Archive Site
  • toxicity [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Toxicity of combined treatment for TB and HIV infections - the established DAIDS/ACTG toxicity grading scale of clinical and laboratory toxicities will be used.
  • CD4 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    CD4 response (mean CD4 rise from baseline)
  • HIV RNA [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    HIV RNA response (% < 50 copies/ml at week 12, 24 and 48)
  • genotypic resistant [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The emergence of NRTI and/or lopinavir genotypic resistant and its clinically
Same as current
Not Provided
Not Provided
 
Pharmacokinetics (PK) and Safety of 2 Different Doses of Lopinavir/Ritonavir in in HIV/Tuberculosis (TB) Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy
A Pilot Study of the Pharmacokinetics and Safety of Lopinavir/Ritonavir 400/100mg Bid Versus Lopinavir/Ritonavir 600/150 mg BID Combined With Nucleoside Analogue Reverse Transcriptase Inhibitors in HIV/TB Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

To assess safety, efficacy and impact of Lopinavir/ritonavir 400/100mg bid or Lopinavir/ritonavir 600/150mg bid in combination with rifampicin-containing anti-TB therapy.

Fixed dose combination of d4T+3TC+NVP (GPOvir) is widely used in Thai HIV infected since June 2002. The prevalence of NNRTI resistance has increased since 2005. Tuberculosis can develop following NNRTI-based regimen failure or after introduction of a new salvage regimen with a boosted PI (immune recovery syndrome). Although, Efavirenz based HAART is preferred in TB/HIV with rifampicin containing antituberculosis. However, Efavirenz could not be used in case of NNRTI failure, intolerance or toxicity. It remains unknown how to optimally treat HIV /TB in populations in which rifampicin has to be used. Moreover, Rifabutin which is recommended when use concomitant with boosted PI4, 5, is not feasible in Thailand and other developing countries due to cost, toxicity and dosing considerations. If ritonavir-boosted LPV demonstrates suitable pharmacokinetics, and is well tolerated, this regimen might prove extremely useful and could be widely implemented. LPV/r is potent and widely available boosted PI in National Health System in Thailand. We therefore believe that there is a strong rationale and impetus for the study of LPV/r 400/100 mg bid versus LPV/r 600/150 mg 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 .

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
  • HIV Infections
  • Tuberculosis
Drug: LPV/r
LPV/r 400/100 mg BID + 2 NRTI for arm 1 (total 48 weeks) LPV/r 600/150 mg BID + 2 NRTI for arm 2 (total 48 weeks)
  • Experimental: 1
    boosted LPV/r 400/100 mg BID + 2 NRTI
    Intervention: Drug: LPV/r
  • Experimental: 2
    boosted LPV/r 600/150 mg BID + 2 NRTI
    Intervention: Drug: LPV/r
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
December 2015
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Confirmed HIV positive after voluntary counseling and testing
  2. Aged >18-60years of age
  3. ARV naïve and NNRTI failure ( PI naive)
  4. CD4+ cell count of <350 cells/mm3 at the time of diagnosed TB
  5. ALT <5 times ULN
  6. Serum creatinine <1.4 mg/dl
  7. Hemoglobin >8 mg/L
  8. TB is diagnosed and planned to receive stable doses of rifampicin-containing anti-TB therapy for at least a 2 week period after initiation of ART
  9. No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
  10. Able to provide written informed consent

Exclusion Criteria:

  1. Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
  2. Current use of any prohibited medications related to drug pharmacokinetics.
  3. 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.
  4. Unlikely to be able to remain in follow-up for the protocol defined period.
  5. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
  6. Karnofsky performance score <30%
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01138202
HIV-NAT 104
No
The HIV Netherlands Australia Thailand Research Collaboration
The HIV Netherlands Australia Thailand Research Collaboration
Department of Disease Control, Ministry of Public Health Thailand
Principal Investigator: Anchalee Avihingsanon, MD The HIV Netherlands Australia Thailand Research Collaboration
The HIV Netherlands Australia Thailand Research Collaboration
March 2015

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