Human Immunodeficiency VirusPUSHNCT02063880
Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART)
A study testing Urgent ART and Early ART in people with Human Immunodeficiency Virus and Immune Reconstitution Inflammatory Syndrome, run by University of Washington at 4 sites in Kenya.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 12 years
- Conditions the study is for
- Human Immunodeficiency Virus, Immune Reconstitution Inflammatory Syndrome
- What is being tested?
- Urgent ART and Early ART
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 183 participants
- Where
- 4 sitesKenya
- Study dates
- Mar 2013to Nov 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Suspected meningitis, any other central nervous system infection, or encephalitis
Trial locations and contacts
4 sites in 1 country.
Kenya4 sites
JOOTRH
Kisumu
Kisumu District Hospital
Kisumu
Mbagathi District Hospital
Nairobi, 0202
Kenyatta National Hospital
Nairobi
About this study
Official title: 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.
Read more
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:
- 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).
- 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.
Read the detailed description
Children will be followed and compared for 6-month mortality.
- Being tested
- Urgent ART, Early ART
- Keywords
- HIV-1, IRIS
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Immune Reconstitution Inflammatory Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Urgent ARTOther
Also called HAART regimens recommended by WHO and Kenya MOH.
Children will be started on HAART <48 hours after enrollment.
Early ARTOther
Children will be started on ART after stabilization 7-14 days after enrollment.
| Study group | Role | What they receive |
|---|---|---|
| Urgent ART | Experimental | Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment.
Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Receives: Other: Urgent ART |
| Early ART | Active comparator | Initiation of HAART 7-14 days after enrollment. Receives: Other: Early ART |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause Mortality
Measured: 6 months post-HAART initiation
Secondary outcomes (2)
Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)
Confirmed, possible or likely IRIS based on external independent review
Measured: 6 months post-HAART initiation
Number of Participants With Potential Drug Toxicity
Participants with adverse events that are deemed to be potentially related to medications.
Measured: 6 months post-HAART initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2014 (estimated)
- Study startMar 2013
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nairobi, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Grace John-Stewart, University of Washington
- Investigators
- Grace John Stewart, MD, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02063880
- Sponsor's protocol ID
- STUDY00001052
- Other IDs
- 2R01HD023412-21
- Acronym
- PUSH
- Status last verified
- Apr 2018
- First submitted
- 21 Aug 2012
- Last updated
- 14 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: after primary and secondary outcomes are published
Publications
Cherkos AS, Cranmer LM, Njuguna I, LaCourse SM, Mugo C, Moraa H, Maleche-Obimbo E, Enquobahrie DA, Richardson BA, Wamalwa D, John-Stewart G. Effect of tuberculosis-HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy. AIDS. 2024 Mar 15;38(4):579-588. doi: 10.1097/QAD.0000000000003797. Epub 2023 Nov 27.
PubMed 38016160Njuguna IN, Cranmer LM, Wagner AD, LaCourse SM, Mugo C, Benki-Nugent S, Richardson BA, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart G. Brief Report: Cofactors of Mortality Among Hospitalized HIV-Infected Children Initiating Antiretroviral Therapy in Kenya. J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):138-144. doi: 10.1097/QAI.0000000000002012.
PubMed 31095004LaCourse SM, Cranmer LM, Njuguna IN, Gatimu J, Stern J, Maleche-Obimbo E, Walson JL, Wamalwa D, John-Stewart GC, Pavlinac PB. Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human Immunodeficiency Virus-Infected Children. Clin Infect Dis. 2018 May 17;66(11):1798-1801. doi: 10.1093/cid/ciy011.
PubMed 29324985Njuguna IN, Cranmer LM, Otieno VO, Mugo C, Okinyi HM, Benki-Nugent S, Richardson B, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart GC. Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial. Lancet HIV. 2018 Jan;5(1):e12-e22. doi: 10.1016/S2352-3018(17)30167-4. Epub 2017 Nov 14.
PubMed 29150377Wagner AD, Njuguna IN, Andere RA, Cranmer LM, Okinyi HM, Benki-Nugent S, Chohan BH, Maleche-Obimbo E, Wamalwa DC, John-Stewart GC. Infant/child rapid serology tests fail to reliably assess HIV exposure among sick hospitalized infants. AIDS. 2017 Jul 17;31(11):F1-F7. doi: 10.1097/QAD.0000000000001562.
PubMed 28609404Njuguna IN, Wagner AD, Cranmer LM, Otieno VO, Onyango JA, Chebet DJ, Okinyi HM, Benki-Nugent S, Maleche-Obimbo E, Slyker JA, John-Stewart GC, Wamalwa DC. Hospitalized Children Reveal Health Systems Gaps in the Mother-Child HIV Care Cascade in Kenya. AIDS Patient Care STDS. 2016 Mar;30(3):119-24. doi: 10.1089/apc.2015.0239.
PubMed 27308805
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urgent Versus Post-Stabilization ART in HIV-1 Infected Children With Severe Co-Infections
- ClinicalTrials.gov ID
- NCT02063880
- Acronym / sponsor ID
- PUSH / STUDY00001052
- Keywords
- HIV-1, IRIS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- University of Nairobi, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Mar 2013
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 17 Feb 2014 (estimated)
- Results
- Posted 25 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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).
- 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.
Detailed description
Children will be followed and compared for 6-month mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Urgent ART | Experimental | Other: Urgent ARTInitiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. |
| Early ART | Active comparator | Other: Early ARTInitiation of HAART 7-14 days after enrollment. |
Who may qualify
- Ages
- Up to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (1 listed)
- Suspected meningitis, any other central nervous system infection, or encephalitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Urgent ARTAlso: HAART regimens recommended by WHO and Kenya MOH.Children will be started on HAART <48 hours after enrollment. | Other | Urgent ART |
| Early ARTChildren will be started on ART after stabilization 7-14 days after enrollment. | Other | Early ART |
Primary outcome
All-cause Mortality
Time frame: 6 months post-HAART initiation
2 secondary outcomes
Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)
Time frame: 6 months post-HAART initiation
Number of Participants With Potential Drug Toxicity
Time frame: 6 months post-HAART initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38016160Cherkos AS, Cranmer LM, Njuguna I, LaCourse SM, Mugo C, Moraa H, Maleche-Obimbo E, Enquobahrie DA, Richardson BA, Wamalwa D, John-Stewart G. Effect of tuberculosis-HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy. AIDS. 2024 Mar 15;38(4):579-588. doi: 10.1097/QAD.0000000000003797. Epub 2023 Nov 27.
- Derived from this study: PubMed 31095004Njuguna IN, Cranmer LM, Wagner AD, LaCourse SM, Mugo C, Benki-Nugent S, Richardson BA, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart G. Brief Report: Cofactors of Mortality Among Hospitalized HIV-Infected Children Initiating Antiretroviral Therapy in Kenya. J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):138-144. doi: 10.1097/QAI.0000000000002012.
- Derived from this study: PubMed 29324985LaCourse SM, Cranmer LM, Njuguna IN, Gatimu J, Stern J, Maleche-Obimbo E, Walson JL, Wamalwa D, John-Stewart GC, Pavlinac PB. Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human Immunodeficiency Virus-Infected Children. Clin Infect Dis. 2018 May 17;66(11):1798-1801. doi: 10.1093/cid/ciy011.
- Derived from this study: PubMed 29150377Njuguna IN, Cranmer LM, Otieno VO, Mugo C, Okinyi HM, Benki-Nugent S, Richardson B, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart GC. Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial. Lancet HIV. 2018 Jan;5(1):e12-e22. doi: 10.1016/S2352-3018(17)30167-4. Epub 2017 Nov 14.
- Derived from this study: PubMed 28609404Wagner AD, Njuguna IN, Andere RA, Cranmer LM, Okinyi HM, Benki-Nugent S, Chohan BH, Maleche-Obimbo E, Wamalwa DC, John-Stewart GC. Infant/child rapid serology tests fail to reliably assess HIV exposure among sick hospitalized infants. AIDS. 2017 Jul 17;31(11):F1-F7. doi: 10.1097/QAD.0000000000001562.
- Derived from this study: PubMed 27308805Njuguna IN, Wagner AD, Cranmer LM, Otieno VO, Onyango JA, Chebet DJ, Okinyi HM, Benki-Nugent S, Maleche-Obimbo E, Slyker JA, John-Stewart GC, Wamalwa DC. Hospitalized Children Reveal Health Systems Gaps in the Mother-Child HIV Care Cascade in Kenya. AIDS Patient Care STDS. 2016 Mar;30(3):119-24. doi: 10.1089/apc.2015.0239.
- Individual participant dataSharing planned: Yes. after primary and secondary outcomes are published
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grace John Stewart, MD, PhD principal investigator
University of Washington
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Urgent ART and Early ART in people with Human Immunodeficiency Virus and Immune Reconstitution Inflammatory Syndrome, run by University of Washington at 4 sites in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause Mortality (time frame: 6 months post-HAART initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02063880, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2018.