Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART) (PUSH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Washington
Sponsor:
Collaborators:
University of Nairobi
Information provided by (Responsible Party):
Grace John-Stewart, University of Washington
ClinicalTrials.gov Identifier:
NCT02063880
First received: August 21, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

Design: Randomized clinical trial involving hospitalized HIV-1 infected children. Children will be randomized to randomized to urgent (<48 hours) versus early antiretroviral therapy (7-14 days). This trial will be unblinded.

Population: Hospitalized HIV-1 infected children who are antiretroviral therapy (ART) naïve ≤ 12 years of age.

Sample size: 360 children will be randomized (180 per arm).

Treatment: All infants will be treated with ART according to World Health Organization (WHO) and Kenyan national guidelines.

Study duration: Enrollment into the study will occur over the course of 36-48 months and each infant will be routinely followed for a maximum of 6 months.

Study site: Kenyan hospitals.

Primary hypothesis:

HIV-1 infected children hospitalized with severe co-infection either may be unsalvageable due to too far advanced immunosuppression/co-infection or may benefit from urgent ART.

Secondary hypotheses:

Urgent ART during an acute infection could potentially result in increased risk of immune reconstitution inflammatory syndrome (IRIS) or drug toxicities/interactions.

Specific aims:

  1. To compare the 6 month all-cause mortality rate, incidence of immune reconstitution inflammatory syndrome (IRIS), and incidence of drug toxicity in HIV-1 infected children (≤ 12 years old) presenting to hospital with a serious infection randomized to urgent (<48 hours) versus early ART (7-14 days).
  2. To determine co-factors for mortality, IRIS, and drug toxicity. Potential cofactors will include: baseline weight-for-age, height-for-age, weight-for-height (Z-scores), CD4, HIV-1 RNA, type of co-infection, age, rate of viral load and CD4 change following ART, immune activation markers, pathogen and HIV-1 specific immune responses.

Secondary aim: To determine etiologies of IRIS and to compare immune reconstitution to HIV, TB, EBV and CMV following ART overall and in each trial arm.


Condition Intervention
Human Immunodeficiency Virus
Immune Reconstitution Inflammatory Syndrome
Other: Urgent ART
Other: Early ART

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Urgent Versus Post-Stabilization ART in HIV-1 Infected Children With Severe Co-Infections

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • All-cause mortality [ Time Frame: 6 months post-HAART initiation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune Reconstitution and Inflammatory Syndrome (IRIS) [ Time Frame: 6 months post-HAART initiation ] [ Designated as safety issue: Yes ]
  • Drug toxicity [ Time Frame: 6 months post-HAART initiation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 360
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Urgent ART

Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment.

Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health.

Other: Urgent ART
Children will be started on HAART <48 hours after enrollment.
Other Name: HAART regimens recommended by WHO and Kenya MOH.
Active Comparator: Early ART
Initiation of HAART 7-14 days after enrollment.
Other: Early ART
Children will be started on ART after stabilization 7-14 days after enrollment.

Detailed Description:

Children will be followed and compared for 6-month mortality.

  Eligibility

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

Inclusion Criteria:

  • Aged ≤ 12 years old (reported)
  • HIV-1 positive (for example, two rapid HIV-1 antibody tests for children >18 months and not breastfeeding, or one HIV-1 DNA/RNA test for children ≤18 months or who are breastfeeding)
  • Not currently receiving antiretroviral therapy (history of pMTCT does not affect eligibility)
  • Eligible to receive ART, according to current WHO guidelines
  • Caregiver plans to reside in study catchment area for at least 6 months (reported)
  • Caregiver provides sufficient locator information

Exclusion Criteria:

  • Suspected meningitis, any other central nervous system infection, or encephalitis
  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: NCT02063880

Contacts
Contact: Dalton Wamalwa, MMed, MPH +011 254 721 239 493 dalton@africaonline.co.ke
Contact: Sarah Benki-Nugent, MS, PhD 206-685-9713 benki@u.washington.edu

Locations
Kenya
Kisumu District Hospital Recruiting
Kisumu, Kenya
Contact: Dalton Wamalwa, MMed         
Principal Investigator: Dalton Wamalwa, MMed         
JOOTRH Recruiting
Kisumu, Kenya
Contact: Dalton Wamalwa, MBChB, MMed, MPH         
Principal Investigator: Dalton Wamalwa, MMed         
Kenyatta National Hospital Recruiting
Nairobi, Kenya
Contact: Dalton Wamalwa, MBChB, MMed, MPH    +254 721-239-493    dalton@africaonline.co.ke   
Principal Investigator: Dalton Wamalwa         
Sponsors and Collaborators
University of Washington
University of Nairobi
Investigators
Principal Investigator: Grace John Stewart, MD, PhD University of Washington
  More Information

No publications provided

Responsible Party: Grace John-Stewart, Professor, Global Health, University of Washington
ClinicalTrials.gov Identifier: NCT02063880     History of Changes
Other Study ID Numbers: 41540-D, 2R01HD023412-21
Study First Received: August 21, 2012
Last Updated: February 14, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board
Kenya: Ethical Review Committee

Keywords provided by University of Washington:
HIV-1
IRIS

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune Reconstitution Inflammatory Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 29, 2014