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

April 11, 2018 updated by: Grace John-Stewart, University of Washington

Urgent Versus Post-Stabilization ART in HIV-1 Infected Children With Severe Co-Infections

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

183

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Kenya
      • Kisumu, Kenya
        • Kisumu District Hospital
      • Kisumu, Kenya
        • JOOTRH
      • Nairobi, Kenya
        • Kenyatta National Hospital
      • Nairobi, Kenya, 0202
        • Mbagathi District Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All-cause Mortality
Time Frame: 6 months post-HAART initiation
6 months post-HAART initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)
Time Frame: 6 months post-HAART initiation
Confirmed, possible or likely IRIS based on external independent review
6 months post-HAART initiation
Number of Participants With Potential Drug Toxicity
Time Frame: 6 months post-HAART initiation
Participants with adverse events that are deemed to be potentially related to medications.
6 months post-HAART initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Nairobi

Investigators

  • Principal Investigator: Grace John Stewart, MD, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

August 21, 2012

First Submitted That Met QC Criteria

February 13, 2014

First Posted (Estimate)

February 17, 2014

Study Record Updates

Last Update Posted (Actual)

May 14, 2018

Last Update Submitted That Met QC Criteria

April 11, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00001052
  • 2R01HD023412-21 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

after primary and secondary outcomes are published

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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