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Monitoring Highly Active Antiretroviral Therapy in HIV-infected Parents in Thailand

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ClinicalTrials.gov Identifier: NCT00162682
Recruitment Status : Completed
First Posted : September 13, 2005
Last Update Posted : January 6, 2012
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Harvard School of Public Health
Information provided by (Responsible Party):
Marc Lallemant, Institut de Recherche pour le Developpement

Tracking Information
First Submitted Date  ICMJE September 7, 2005
First Posted Date  ICMJE September 13, 2005
Last Update Posted Date January 6, 2012
Study Start Date  ICMJE May 2005
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2009)		 Proportion of "clinical failures" defined as confirmed CD4 count below 50/mm3, first or new AIDS-defining event, or death [ Time Frame: After 3 years of follow-up ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2005)		 Proportion of "clinical failures" defined as confirmed CD4 count below 50/mm3, first or new AIDS-defining event, or death
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2009)
  • The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities [ Time Frame: After 3 years of follow-up ]
  • The secondary endpoint related to safety will be time to the first development of grade 3 or grade 4 sign, symptom, and laboratory abnormality. [ Time Frame: During 3 years of follow-up ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2005)		 The number of therapeutic options left taking into account drugs exhausted cross-resistance mutations and shared toxicities
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Monitoring Highly Active Antiretroviral Therapy in HIV-infected Parents in Thailand
Official Title  ICMJE A Phase III, Randomized, Non-inferiority Trial Comparing the Standard Viral Load Based Antiretroviral Monitoring Strategy With a CD4 Based Monitoring Strategy Among Antiretroviral Naive Immunocompromised Adults in Thailand
Brief Summary The purpose of this study is to determine if a decision to switch to a subsequent antiretroviral regimen based upon the CD4 cell count rather than the standard switching strategy based on viral load could ensure the same immunological and clinical outcome and preserve future treatment options in AIDS patients
Detailed Description

Implementation of highly active antiretroviral therapy (HAART) has led to a substantial decrease in HIV-related mortality and morbidity. Current guidelines emphasize maximal and durable viral load suppression. However, while the goal of therapy is the restoration of immunity, treatment failure is usually defined as the inability to maintain undetectable viral load, without regard to immune function. This situation often leads to a rapid sequence of therapeutic switches, thus narrowing therapeutic options over time. A monitoring strategy driven primarily by the patient's immune restoration would most likely be as effective in preventing disease progression, would lead to fewer changes in HAART regimens and would be considerably simpler and cost effective.

Subjects will be randomly assigned to one of two switching strategies:

  • VL-S, the standard viral load (VL) based monitoring strategy, where switching is performed when VL is confirmed (within one month) above 400 copies per mL.
  • CD4-S, the alternative CD4 based monitoring strategy where switching is performed when a confirmed (within one month) relative decline in CD4 count of more than 30% from peak values is observed within 200 cells from baseline.

The initial HAART regimen will be a NNRTI+NRTI containing regimen and the second line regimen will be a PI containing regimen, subsequent regimens will be chosen individually based on tolerance, previous drugs used, resistance profile, and drugs available. Patients will be followed until the end of the study (maximum of 5 years for the first enrollee, three years for the last enrollee).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Procedure: Antiretroviral Drug Combination Switching Criteria
    Antiretroviral treatment will use the standard viral load (VL) based monitoring strategy, where switching is performed when VL is confirmed (within one month) above 400 copies per mL.
  • Procedure: Antiretroviral Drug Combination Switching Criteria
    Antiretroviral treatment is monitored using a CD4 based monitoring strategy where switching is performed when a confirmed (within one month) relative decline in CD4 count of more than 30% from peak values is observed within 200 cells from baseline.
Study Arms  ICMJE
  • Active Comparator: 1
    * VL-S, the standard viral load (VL) based monitoring strategy, where switching is performed when VL is confirmed (within one month) above 400 copies per mL.
    Intervention: Procedure: Antiretroviral Drug Combination Switching Criteria
  • Experimental: 2
    CD4-S, the alternative CD4 based monitoring strategy where switching is performed when a confirmed (within one month) relative decline in CD4 count of more than 30% from peak values is observed within 200 cells from baseline.
    Intervention: Procedure: Antiretroviral Drug Combination Switching Criteria
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 30, 2008)		 716
Original Enrollment  ICMJE
 (submitted: September 7, 2005)		 700
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Eligibility Criteria:

Patients fulfilling the following criteria are eligible:

  • At least 18 years of age
  • Confirmed HIV infection: two positive serology results from two different blood draws are required for documentation of HIV infection.
  • Antiretroviral drug naïve with the exception of short course of antiretrovirals received in the context of the prevention of mother to child HIV transmission
  • Need for antiretroviral treatment
  • Willingness to receive a long-term treatment for the HIV infection, according to the study schedule at the participating site
  • Signed informed consent to participate in the study (the patient's legal guardian may give his/her consent if the patient cannot provide consent)
  • Does not present an exclusion criteria to the knowledge of the site investigator

Inclusion Criteria:

Eligible patients fulfilling the following criteria can be enrolled in the study:

  • Meeting all eligibility criteria
  • Two CD4+ cell counts between 50 and 250 cells/mm3 performed within the last six months before enrolment (CD4 cell count should be assessed at least 2 weeks apart from any acute infection)
  • Willingness to modify antiretroviral therapy in accordance with the randomized switching scheme assignment
  • Subject understands that study drugs will be supplied for free by the study only during participation in the study. After discontinuation of the study, patients will be taken care of in the National ARV Access Program.

Exclusion Criteria:

  • For women, pregnancy
  • For women of child bearing potential, lack of willingness to follow an effective method of contraception (in case, during the study, a woman wants to become pregnant or becomes pregnant, she should inform the physician immediately for best therapeutic decision)
  • Chronic hepatitis B or C
  • Acute hepatitis within 30 days of study entry.
  • Acute HIV infection, as it can be established with the date of last negative serology less than one year before enrollment and the history of the patient disease
  • Co-enrollment in another study without prior written agreement of the study team
  • Psycho-social environment or condition which, in the physician's opinion, makes adherence to the protocol highly unlikely.
  • Pre-existing diabetes mellitus (prior gestational diabetes is allowed).
  • The following laboratory values: hemoglobin < 8.0 mg/dl, absolute neutrophil count < 1000 cells/mm3, ALT, AST or total bilirubin value > 5.0 x ULN, serum creatinine > 1.0 x ULN, platelet count < 50,000/mm3, pancreatic amylase >2.0 x ULN or lipase > 2.0 X ULN, or total amylase > 2.0 X ULN plus symptoms of pancreatitis.
  • Severe illness, grade 3 or 4 laboratory exam values not resolved within one month of enrollment without previous agreement of the PHPT attending physician
  • Any clinically significant condition (other than HIV infection) which, in the investigator's opinion, would interfere with the conduct of the study.
  • Current active substance or alcohol abuse that would interfere with participation in the study.
  • Condition(s) that contraindicate all the first line regimens proposed in this study.
  • Chemotherapy for active malignancy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00162682
Other Study ID Numbers  ICMJE R01HD042964( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marc Lallemant, Institut de Recherche pour le Developpement
Study Sponsor  ICMJE Institut de Recherche pour le Developpement
Collaborators  ICMJE
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Harvard School of Public Health
Investigators  ICMJE
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpement & Harvard School of Public Health
PRS Account Institut de Recherche pour le Developpement
Verification Date January 2012

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