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Safety of Raltegravir When Given as Part of HIV Therapy in HIV/HCV Coinfected Individuals

This study is not yet open for participant recruitment.
Verified June 2012 by University of Hawaii
Sponsor:
Collaborator:
University of Oxford
Information provided by (Responsible Party):
University of Hawaii
ClinicalTrials.gov Identifier:
NCT01147107
First received: June 16, 2010
Last updated: June 14, 2012
Last verified: June 2012
History of Changes
  Purpose

This study will assess the virologic efficacy and risk of liver toxicity of raltegravir-based regimens in HIV/HCV co-infected individuals, particularly in those starting ARV at lower CD4 counts. As HIV/HCV co-infection is a relatively common event in many parts of the world where intravenous substance abuse is a significant risk factor for HIV transmission, more data regarding these issues are important to obtain.


Condition Intervention Phase
HIV/ Hepatitis C Co-Infection
 Drug: Raltegravir (Isentress)
Drug: Efavirenz (Sustiva)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label, Randomized, Pilot Study of the Efficacy and Hepatic Safety of Raltegravir-based and Efavirenz-based Regimens When Given in Combination With Tenofovir and Emtricitabine in Antiretroviral-Naive HIV-infected Subjects Co-Infected With Hepatitis C

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Hawaii:

Primary Outcome Measures:
  • Plasma HIV RNA </= 50 copies/mL [ Time Frame: 24 and 72 weeks ] [ Designated as safety issue: No ]
    The rates of HIV virologic suppression (plasma HIV RNA < 50 copies/mL) at week 24 and 72 of study in the two arms of the study will be estimated.

  • Grade 2 and higher alanine aminotransferase (ALT) elevations [ Time Frame: over week 72 ] [ Designated as safety issue: Yes ]

    To estimate the rates of grade 2*and higher ALT elevations in the two regimens.

    * grade 2 = ALT elevations 2.6-5.0 x upper limit of normal [ULN]; grade 3 = ALT 5.1-10.0 x ULN; grade 4 = >10.0 x ULN



Secondary Outcome Measures:
  • CD4 count [ Time Frame: to week 24 and to week 72 ] [ Designated as safety issue: No ]
    To estimate the rates of HIV virologic suppression (plasma HIV RNA < 50 copies/mL) at week 24 and 72 of study in raltegravir-based and efavirenz-based regimens when given in combination with tenofovir and emtricitabine in anti-retroviral-naïve HIV-infected subjects co-infected with hepatitis C.

  • Overall safety and tolerability [ Time Frame: over 72 weeks ] [ Designated as safety issue: Yes ]
    To assess overall safety and tolerability of the two regimens

  • metabolic parameters [ Time Frame: over 24 weeks and over 72 weeks ] [ Designated as safety issue: No ]
    To assess changes in metabolic parameters (glucose, insulin resistance, total, LDL and HDL cholesterol, triglycerides) from entry to week 24 and from entry to week 72 in the two arms

  • adherence [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To assess adherence in the two arms

  • HIV/HCV viral dynamics [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To characterize HIV/HCV viral dynamics in plasma and in circulating cells of monocytic and lymphocytoic lineage in response to HIV therapy; to assess the dynamic relationship between these compartment and their relationship with clinical outcomes and with markers of immune reconstitution and immune activation

  • HIV drug resistance [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To assess patterns of genotypic HIV drug resistance associated with virologic failure

  • AIDS related mortality/morbidity [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To examine time to death and/or occurrence of AIDS-defining events in the two arms

  • Time to change in therapy [ Time Frame: Over 72 weeks ] [ Designated as safety issue: Yes ]
    To assess time to change in randomly assigned therapy in the two arms

  • Clinical outcome (in relationship to liver fibrosis stage) [ Time Frame: over 72 weeks ] [ Designated as safety issue: No ]
    To examine the impact of liver fibrosis stage (as calculated by Fib-4 index of liver fibrosis [1]) on changes in plasma HIV RNA and in CD4 count, rates of ALT elevations, overall safety and tolerability, changes in metabolic parameters*, adherence, HCV viral load*, time to death/AIDS-defining events and change in randomly assigned therapy


Estimated Enrollment: 80
Study Start Date: December 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir based therapy
Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily
 Drug: Raltegravir (Isentress)
Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily
Active Comparator: Efavirenz based therapy
Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
 Drug: Efavirenz (Sustiva)
Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection by licensed diagnostic test per WHO
  • CD4 count less than 250 cells/mm3 and/or WHO stage III or IV disease
  • Hepatitis C infection as documented by positive Hepatitis C antibodies
  • Willingness for both males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.
  • Age greater or equal to 18 years
  • Ability and willingness to provide written informed consent
  • The following laboratory parameters documented within 30 days prior to study entry:

oHemoglobin greater or equal to 9.0 oAbsolute neutrophil count greater or equal to 500/μL oPlatelet count greater or equal to 40,000/μL oAST (SGOT) and ALT (SGPT) less than 2x ULN oCreatinine less than or equal to 1.5 x ULN

-Estimated creatinine clearance greater than 60 mL/min

Exclusion Criteria:

  • Any prior antiretroviral therapy.
  • Any previously known hypersensitivity to components of the study drug formulations.
  • Positive Hepatitis B surface antigen
  • Prior history of hepatitis C therapy, or intent to undergo hepatitis C therapy during the 72 week period of study
  • Any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.
  • Any vaccination within 30 days of study entry.
  • Requirement for therapy for active tuberculosis during the duration of study
  • Anticipated need for rifampin during the course of the study
  • Requirement for acute therapy for other AIDS-defining illness or other serious medical illnesses (in the opinion of the site investigator) within 14 days prior to study entry unless subject has completed at least 14 days of therapy and is assessed to be clinically stable.
  • Malignancy requiring systemic chemotherapy.
  • Other chronic illnesses including diabetes, autoimmune diseases, and endocrinopathies, except subjects on stable physiologic replacement therapy for low testosterone or thyroid levels
  • Any condition which, in the opinion of the investigator, would compromise the subject's ability to participate in the study
  • Current substance abuse
  • Pregnancy or breast-feeding.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01147107

Contacts
Contact: Thuy Le, MD 84-8-838-2338

Locations
Vietnam
Hospital for Tropical Diseases Not yet recruiting
Ho Chi Minh City, Vietnam
Contact: Thuy Le, M.D.     84-8-838 2338        
Principal Investigator: Thuy Le, M.D.            
Sub-Investigator: Tuan Huynh, M.D.            
Sponsors and Collaborators
University of Hawaii
University of Oxford
Investigators
Principal Investigator: Cecilia Shikuma, MD University of Hawaii at Manoa
Study Chair: Chinh T Nguyen, MD, PhD Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Study Chair: Jeremy Farrar, MD PhD Oxford University Clinical Research Unit
Study Director: Thuy Le, MD University of Hawaii, Oxford University Clinical Research Unit
  More Information

No publications provided

Responsible Party: University of Hawaii
ClinicalTrials.gov Identifier: NCT01147107     History of Changes
Other Study ID Numbers: VHARP 001
Study First Received: June 16, 2010
Last Updated: June 14, 2012
Health Authority: Vietnam: Vietnam Ministry of Health

Keywords provided by University of Hawaii:
HIV/HCV co-infection
Antiretroviral therapy

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Tenofovir
 Efavirenz
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 23, 2013