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

• ClinicalTrials.gov Identifier: NCT02063880
• Recruitment Status: Completed
• First Posted: February 17, 2014
• Results First Posted: July 25, 2017
• Last Update Posted: May 14, 2018
• Sponsor: University of Washington
• Collaborators: University of Nairobi; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Grace John-Stewart, University of Washington

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Human Immunodeficiency Virus; Immune Reconstitution Inflammatory Syndrome
• Interventions: Other: Urgent ART; Other: Early ART
• Enrollment: 183

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Urgent ART	Early ART
Arm/Group Description	Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Urgent ART: Children will be started on HAART <48 hours after enrollment.	Initiation of HAART 7-14 days after enrollment. Early ART: Children will be started on ART after stabilization 7-14 days after enrollment.
Period Title: Overall Study
Started	90	93
Completed	62	66
Not Completed	28	27
Reason Not Completed
Death	21	18
Lost to Follow-up	7	7
Ineligible	0	2

Baseline Characteristics

Arm/Group Title		Urgent ART	Early ART	Total
Arm/Group Description		Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Urgent ART: Children will be started on HAART <48 hours after enrollment.	Initiation of HAART 7-14 days after enrollment. Early ART: Children will be started on ART after stabilization 7-14 days after enrollment.	Total of all reporting groups
Overall Number of Baseline Participants		90	91	181
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	90 participants	91 participants	181 participants
		2; (0.9 to 6)	1.8; (0.8 to 4.5)	1.9; (0.8 to 4.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	90 participants	91 participants	181 participants
	Female	40 44.4%	41 45.1%	81 44.8%
	Male	50 55.6%	50 54.9%	100 55.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Kenya	Number Analyzed	90 participants	91 participants	181 participants
		90	91	181
CD4%; Median (Inter-Quartile Range); Unit of measure: %
	Number Analyzed	90 participants	91 participants	181 participants
		12.5; (9 to 18.3)	17; (9 to 24)	14.5; (9 to 22)

Outcome Measures

1. Primary Outcome

Title	All-cause Mortality
Description	[Not Specified]
Time Frame	6 months post-HAART initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Urgent ART	Early ART
Arm/Group Description:	Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Urgent ART: Children will be started on HAART <48 hours after enrollment.	Initiation of HAART 7-14 days after enrollment. Early ART: Children will be started on ART after stabilization 7-14 days after enrollment.
Overall Number of Participants Analyzed	90	91
Measure Type: Number; Unit of Measure: participants
	21	18

2. Secondary Outcome

Title	Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)
Description	Confirmed, possible or likely IRIS based on external independent review
Time Frame	6 months post-HAART initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Urgent ART	Early ART
Arm/Group Description:	Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Urgent ART: Children will be started on HAART <48 hours after enrollment.	Initiation of HAART 7-14 days after enrollment. Early ART: Children will be started on ART after stabilization 7-14 days after enrollment.
Overall Number of Participants Analyzed	90	91
Measure Type: Number; Unit of Measure: participants
	10	12

3. Secondary Outcome

Title	Number of Participants With Potential Drug Toxicity
Description	Participants with adverse events that are deemed to be potentially related to medications.
Time Frame	6 months post-HAART initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Urgent ART	Early ART
Arm/Group Description:	Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Urgent ART: Children will be started on HAART <48 hours after enrollment.	Initiation of HAART 7-14 days after enrollment. Early ART: Children will be started on ART after stabilization 7-14 days after enrollment.
Overall Number of Participants Analyzed	90	91
Measure Type: Number; Unit of Measure: participants
	23	15

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Urgent ART		Early ART
Arm/Group Description	Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health. Urgent ART: Children will be started on HAART <48 hours after enrollment.		Initiation of HAART 7-14 days after enrollment. Early ART: Children will be started on ART after stabilization 7-14 days after enrollment.
All-Cause Mortality
	Urgent ART		Early ART
	Affected / at Risk (%)		Affected / at Risk (%)
Total	21/90 (23.33%)		18/91 (19.78%)
Serious Adverse Events
	Urgent ART		Early ART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/90 (37.78%)		40/91 (43.96%)
Infections and infestations
Non-mortality SAE	13/90 (14.44%)	13	22/91 (24.18%)	22
Mortality	21/90 (23.33%)	21	18/91 (19.78%)	18
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Urgent ART		Early ART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/90 (11.11%)		12/91 (13.19%)
Blood and lymphatic system disorders
IRIS	10/90 (11.11%)	10	12/91 (13.19%)	12

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Grace John-Stewart
• Organization: University of Washington
• Phone: 206 5434278
• EMail: gjohn@uw.edu

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

Njuguna 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.

LaCourse 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.

Njuguna 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.

Wagner 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.

Njuguna 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.

• Responsible Party: Grace John-Stewart, University of Washington
• ClinicalTrials.gov Identifier: NCT02063880
• Other Study ID Numbers: STUDY00001052; 2R01HD023412-21 ( U.S. NIH Grant/Contract )
• First Submitted: August 21, 2012
• First Posted: February 17, 2014
• Results First Submitted: May 1, 2017
• Results First Posted: July 25, 2017
• Last Update Posted: May 14, 2018