When to Start Anti-HIV Drugs in Children Infected With HIV (The PREDICT Study)

This study has been completed.
Sponsor:
Collaborator:
Comprehensive International Program of Research on AIDS
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00234091
First received: October 4, 2005
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to determine when HIV infected children should begin taking anti-HIV medications in order to improve both patient quality of life and survival.


Condition Intervention Phase
HIV Infections
Drug: Abacavir
Drug: Efavirenz
Drug: Lamivudine
Drug: Lopinavir/Ritonavir
Drug: Nelfinavir
Drug: Nevirapine
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Randomized Study to Compare Antiretroviral Therapy (ART) Initiation When CD4 is Between 15% to 24% to ART Initiation When CD4 Falls Below 15% in Children With HIV Infection and Moderate Immune Suppression

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • AIDS-free survival [ Time Frame: Week 144 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Direct and indirect cost of treatment per patient [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
  • Number and duration of hospitalizations [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Time to and number of Grades 3 or 4 HAART-related toxicity and intolerance [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]
  • Number of HAART regimen changes [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Number of Grades 1 or 2 infectious episodes [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Number of courses of antibiotics used [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Number of HIV-related clinical events [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Virologic failure, defined as HIV viral load of 1000 copies/ml [ Time Frame: Week 24 after HAART initiation ] [ Designated as safety issue: No ]
  • Presence of a resistance mutation in participants with virologic failure [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Change of growth in Z scores [ Time Frame: study entry to Week 144 ] [ Designated as safety issue: No ]
  • Change in CD4% and time-weighted average change [ Time Frame: study entry and Week 144 ] [ Designated as safety issue: No ]
  • CD4 less than 10% [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
  • Average scores of the child's quality of life over time [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
  • Percentage adherence to HAART over time by pill count/weighing liquid medication bottles, self report, and questionnaire [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Presence of iron deficiency anemia [ Time Frame: study entry and Weeks 24, 48, 72, 96, 120, and 144 ] [ Designated as safety issue: No ]
  • HIV viral sequence [ Time Frame: study entry and treatment failure ] [ Designated as safety issue: No ]
  • HIV viral replication capacity [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Cytotoxic T-cell (CTL) response [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Percentage of different T-cell subsets [ Time Frame: study entry and Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]

Enrollment: 300
Study Start Date: April 2006
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Immediate treatment; individuals receive HAART on Day 1 of the study
Drug: Abacavir
8 mg/kg (up to 300 mg/dose) take orally twice daily
Drug: Efavirenz
200 to 600 mg taken orally once daily
Drug: Lamivudine
4 mg/kg (up to 150 mg/dose) taken orally twice daily
Drug: Lopinavir/Ritonavir
230 mg/57.5 mg/m^2 body surface area taken orally twice daily with food
Drug: Nelfinavir
45-55 mg/kg taken orally twice daily with food
Drug: Nevirapine
120 mg/m^2 once daily for first 14 days, tehn 200 mg/m^2 (up to 400 mg/day) twice daily
Drug: Zidovudine
180-240 mg/m^2 every 12 hours (up to 300 mg/dose)
Active Comparator: 2
Delayed treatment; individuals receive HAART if their CD4 percentage falls below 15 percentage OR if they develop a CDC category C illness
Drug: Abacavir
8 mg/kg (up to 300 mg/dose) take orally twice daily
Drug: Efavirenz
200 to 600 mg taken orally once daily
Drug: Lamivudine
4 mg/kg (up to 150 mg/dose) taken orally twice daily
Drug: Lopinavir/Ritonavir
230 mg/57.5 mg/m^2 body surface area taken orally twice daily with food
Drug: Nelfinavir
45-55 mg/kg taken orally twice daily with food
Drug: Nevirapine
120 mg/m^2 once daily for first 14 days, tehn 200 mg/m^2 (up to 400 mg/day) twice daily
Drug: Zidovudine
180-240 mg/m^2 every 12 hours (up to 300 mg/dose)

Detailed Description:

The use of highly active antiretroviral therapy (HAART) has resulted in a significant reduction in AIDS-related deaths and complications among adults and adolescents. However, the medical management of HIV infected children remains challenging. Access to HIV treatment is limited and early treatment initiation can cause serious complications. Since there is currently no cure for HIV, a balance between treating the disease and maintaining quality of life must be weighed carefully. An evaluation to determine the appropriate time to initiate HAART is necessary to improve both quality of life and survival for HIV infected children.

This study will last 144 weeks. All participants will have a CD4 percentage (CD4%) between 15% and 24% and will be randomly assigned to either receive immediate or delayed HAART. The HAART regimen will consist of two nucleoside reverse transcriptase inhibitors, zidovudine and lamivudine. In addition, participants will also receive either one non-nucleoside reverse transcriptase inhibitor, nevirapine or efavirenz, or one protease inhibitor, ritonavir-boosted lopinavir or nelfinavir. Abacavir will replace zidovudine or lamivudine if participants experience toxicity to the regimen. Participants in the immediate treatment arm will receive HAART on Day 1 of the study regardless of their CD4%. Participants in the delayed treatment arm will receive HAART if their CD4% falls below 15 or if they develop a CDC Category C illness.

Study visits will occur every 4 weeks for the first 12 weeks and then every 12 weeks until the end of the study. Blood collection, physical exams, and medical and medication history reviews will occur at all visits. Adherence, quality of life, and lipodystrophy assessments will occur every 12 weeks for participants on HAART. Participants will be encouraged to enroll in a related substudy to examine the neurodevelopment of HIV infected children.

  Eligibility

Ages Eligible for Study:   1 Year to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected
  • Antiretroviral naive, defined as never receiving anti-HIV medications, receiving them for less than 7 days, or only receiving them to prevent mother-to-child transmission (MTCT)
  • CD4% between 15 and 24 within 30 days prior to study entry
  • CDC pediatric clinical classification A or B
  • Parent or guardian willing to provide informed consent and willing to follow all study procedures and requirements

Exclusion Criteria:

  • Use of systemic chemotherapy, immunomodulators, HIV vaccines, immune globulin, interleukins, or interferons within 30 days prior to study entry
  • Active AIDS-defining illnesses (CDC Category C) within 30 days prior to study entry
  • Certain abnormal laboratory values
  • Known kidney disease
  • Known allergy or sensitivity to study drugs
  • Require certain medications
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00234091

Locations
Cambodia
National Pediatric Hosp., Cambodia CIPRA CRS
Phnom Penh, Cambodia
Social Health Clinic, Cambodia CIPRA CRS
Phnom Penh, Cambodia
Thailand
Hiv-Nat Cipra Crs
Pathumwan, Bangkok, Thailand, 10330
Chiang Rai Regional Hosp. CIPRA CRS
Muang, Chiang Rai, Thailand, 57000
Prapokklao Hosp. CIPRA CRS
Chantaburi, Thailand, 22000
Nakornping Hosp. CIPRA CRS
Chiang Mai, Thailand, 50180
Queen Savang Vadhana Memorial Hosp. CIPRA CRS
Chonburi, Thailand, 20110
Srinagarind Hosp. CIPRA CRS
Khon Kaen, Thailand, 40002
Bamrasnaradura Institute CIPRA CRS
Nonthaburi, Thailand, 11000
Sponsors and Collaborators
Comprehensive International Program of Research on AIDS
Investigators
Study Chair: Kiat Ruxrungtham, MD, MPH Department of Medicine at Chulalongkorn University, Bangkok, Thailand
Study Chair: Saphonn Vonthanak, MD, PhD National Center for HIV/AIDS, Dermatology, and STDs, Phnom Penh, Cambodia
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00234091     History of Changes
Other Study ID Numbers: CIPRA TH001, PREDICT, 10409
Study First Received: October 4, 2005
Last Updated: December 2, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive
Treatment Initiation
Infant
Preschool Child
Child
Zidovudine
AZT
Retrovir
3TC
Lamivudine
Epivir
Nevirapine
NVP
Viramune
Efavirenz
EFV
Sustiva
Lopinavir/Ritonavir
LPV/r
Kaletra
Nelfinavir
NFV
Viracept
ABC
Abacavir
Ziagen

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine
Lamivudine
Efavirenz
Abacavir
Ritonavir
Nelfinavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 20, 2014