Novel Use Of Hydroxyurea in an African Region With Malaria (NOHARM)

• ClinicalTrials.gov Identifier: NCT01976416
• Recruitment Status: Completed
• First Posted: November 5, 2013
• Results First Posted: October 1, 2018
• Last Update Posted: December 4, 2018
• Sponsor: Indiana University
• Collaborators: Doris Duke Charitable Foundation; Makerere University; Mulago Hospital, Uganda; Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Chandy John, Indiana University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Sickle Cell Anemia; Sickle Cell Disease; Malaria
• Interventions: Drug: Hydroxyurea; Drug: Placebo
• Enrollment: 208

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Hydroxyurea	Placebo
Arm/Group Description	Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Hydroxyurea	Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Placebo
Period Title: Overall Study
Started	104	104
Completed	102	102
Not Completed	2	2

Baseline Characteristics

Arm/Group Title		Hydroxyurea	Placebo	Total
Arm/Group Description		Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Hydroxyurea	Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Placebo	Total of all reporting groups
Overall Number of Baseline Participants		104	103	207
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age 1.00-3.99 years	Number Analyzed	104 participants	103 participants	207 participants
		104 100.0%	103 100.0%	207 100.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	104 participants	103 participants	207 participants
	Female	49 47.1%	46 44.7%	95 45.9%
	Male	55 52.9%	57 55.3%	112 54.1%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Uganda	Number Analyzed	104 participants	103 participants	207 participants
		104	103	207

Outcome Measures

1. Primary Outcome

Title	Number of Malaria Episodes
Description	Malaria is defined as the presence of P. falciparum or P. malariae on the peripheral smear of any child brought in for medical evaluation of fever. P. vivax, P. ovale and P. knowlesi are not known to be present in this region, but if a child is seen with suspected infection with any of these malaria parasites, this will also be recorded as a case of malaria. Incidence will be reported in the number of cases per 100 patient years.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea	Placebo
Arm/Group Description:	Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Hydroxyurea	Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Placebo
Overall Number of Participants Analyzed	104	103
Overall Number of Units Analyzed; Type of Units Analyzed: Person-years	104	103
Measure Type: Number; Unit of Measure: malaria episodes
	5	7

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Hydroxyurea		Placebo
Arm/Group Description	Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Hydroxyurea		Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months Placebo
All-Cause Mortality
	Hydroxyurea		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	2/104 (1.92%)		1/103 (0.97%)
Serious Adverse Events
	Hydroxyurea		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/104 (5.77%)		6/103 (5.83%)
Blood and lymphatic system disorders
Vaso-Occlusive Crisis † 1	0/104 (0.00%)	0	1/103 (0.97%)	1
Acute Splenic Squestration † 1	2/104 (1.92%)	2	0/103 (0.00%)	0
Anemia † 1	0/104 (0.00%)	0	1/103 (0.97%)	1
General disorders
Sudden Death † 1	1/104 (0.96%)	1	0/103 (0.00%)	0
Infections and infestations
Bacteremia † 1	2/104 (1.92%)	2	2/103 (1.94%)	2
Respiratory, thoracic and mediastinal disorders
Pneumonia † 1	1/104 (0.96%)	1	2/103 (1.94%)	2
1 Term from vocabulary, MedDRA (10.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Hydroxyurea		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/104 (73.08%)		88/103 (85.44%)
Blood and lymphatic system disorders
Vaso-Occlusive Crisis † 1	38/104 (36.54%)	58	59/103 (57.28%)	106
Malaria † 1	3/104 (2.88%)	5	7/103 (6.80%)	7
Anemia † 1	25/104 (24.04%)	40	42/103 (40.78%)	65
Thrombocytopenia † 1	11/104 (10.58%)	12	4/103 (3.88%)	4
Gastrointestinal disorders
Gastrointestinal-related † 1	13/104 (12.50%)	15	12/103 (11.65%)	15
Infections and infestations
Clinical Sepsis † 1	6/104 (5.77%)	8	13/103 (12.62%)	16
Other infections † 1	7/104 (6.73%)	8	14/103 (13.59%)	14
Injury, poisoning and procedural complications
Others (e.g., injury) † 1	7/104 (6.73%)	7	9/103 (8.74%)	10
Respiratory, thoracic and mediastinal disorders
Pneumonia † 1	21/104 (20.19%)	24	24/103 (23.30%)	32
Upper Respiratory Tract Infection † 1	54/104 (51.92%)	107	62/103 (60.19%)	108
1 Term from vocabulary, MedDRA (10.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr Chandy John
• Organization: Indiana University
• Phone: 317-274-8940
• EMail: chjohn@iu.edu

Publications of Results:

Opoka RO, Ndugwa CM, Latham TS, Lane A, Hume HA, Kasirye P, Hodges JS, Ware RE, John CC. Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia. Blood. 2017 Dec 14;130(24):2585-2593. doi: 10.1182/blood-2017-06-788935. Epub 2017 Oct 19.

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

Carman AS, Sautter C, Anyanwu JN, Ssemata AS, Opoka RO, Ware RE, Rujumba J, John CC. Perceived benefits and risks of participation in a clinical trial for Ugandan children with sickle cell anemia. Pediatr Blood Cancer. 2020 Feb;67(2):e27830. doi: 10.1002/pbc.27830. Epub 2019 May 28.

Anyanwu JN, Williams O, Sautter CL, Kasirye P, Hume H, Opoka RO, Latham T, Ndugwa C, Ware RE, John CC. Novel Use of Hydroxyurea in an African Region With Malaria: Protocol for a Randomized Controlled Clinical Trial. JMIR Res Protoc. 2016 Jun 23;5(2):e110. doi: 10.2196/resprot.5599.

• Responsible Party: Chandy John, Indiana University
• ClinicalTrials.gov Identifier: NCT01976416
• Other Study ID Numbers: 2012139
• First Submitted: October 22, 2013
• First Posted: November 5, 2013
• Results First Submitted: February 2, 2018
• Results First Posted: October 1, 2018
• Last Update Posted: December 4, 2018