Clinical trial NCT05711485: Platelet-Directed Whole Blood Transfusion Strategy for Malaria
Official title: Clinical and Translational Investigations of Severe Malaria Pathophysiology [Parent Study Protocol]
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Severe Malaria
Thrombocytopenia
Keywords: Malaria
Plasmodium falciparum
Zambia
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: Tropical Diseases Research Centre
name: University of California, San Francisco
name: University of Maryland
First posted: 2023-02-03
Enrollment: 132
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Open-label randomized controlled trial to test the effectiveness of whole blood transfusion for improving survival in children with severe malaria complicated by thrombocytopenia.

Detailed description: The PLATFORM trial is a single-center, open-label randomized controlled trial of whole blood transfusion for severe malaria complicated by thrombocytopenia. The trial will recruit 132 Zambian children 6 months to 15 years old with severe malaria defined according to modified WHO criteria with concomitant thrombocytopenia, defined here as a platelet count ≤75,000/uL, who do not otherwise have a current indication for transfusion according to current guidelines. Children will be randomized 1:1 to whole blood transfusion or no whole blood transfusion and followed to hospital discharge or death. The trial is nested within the Children and Adults with Severe Malaria (CHASM) cohort, a prospective observational study of severe malaria.

Eligibility criteria: Inclusion Criteria:

* Age \<5 years
* Platelet count ≤75,000/uL
* Hemoglobin \>5 and ≤9 g/dL
* P. falciparum parasitemia ≥500 parasites/uL
* Diagnosis of severe malaria meeting World Health Organization (WHO) criteria
* Ability and willingness of the legal guardian to comply with study protocol for the duration of the study
* Residence within health clinic catchment area
* Signed informed consent obtained from the parent or legal guardian of the participant

Exclusion Criteria:

* Residence in foster care or children otherwise under government supervision
* Residence outside the hospital catchment area, or plan to leave the area
* Presence of any other condition or abnormality which, in the opinion of the investigator, would compromise the safety of the participant or the quality of the data
* Any contraindication to whole blood transfusion

Primary outcomes:
measure: Incidence of all-cause mortality
timeFrame: Up to hospital discharge or in-hospital death, up to 28 days on average
Secondary outcomes:
measure: Change in hemoglobin (Hb)
timeFrame: Pre- and post-transfusion, comparing baseline measurements to measurements taken 2 hours after transfusion completion and 24 hours later. For the Control arm, measurements will be made at baseline and Study Hour 6 ±2 and 24 hours later
measure: Change in platelet count
timeFrame: Pre- and post-transfusion, comparing baseline measurements to measurements taken 2 hours after transfusion completion and 24 hours later. For the Control arm, measurements will be made at baseline and Study Hour 6 ±2 and 24 hours later
measure: Change in white blood cell (WBC) count
timeFrame: Pre- and post-transfusion, comparing baseline measurements to measurements taken 2 hours after transfusion completion and 24 hours later. For the Control arm, measurements will be made at baseline and Study Hour 6 ±2 and 24 hours later
measure: Incidence of transfusion reaction
timeFrame: During or after transfusion, up to the day of hospital discharge or in-hospital death, up to 28 days on average
measure: Length of hospitalization
timeFrame: Up to hospital discharge or in-hospital death, up to 28 days on average
measure: Parasite clearance
timeFrame: 0-72 hours, measured every 12±2 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bloomberg School of Public Health
state: Maryland
city: Ndola
country: Zambia
facility: Tropical Diseases Research Centre
state: Copperbelt
Study officials:
affiliation: Johns Hopkins University
name: Matthew M Ippolito, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ippolito MM, Kabuya JB, Hauser M, Kamavu LK, Banda PM, Yanek LR, Malik R, Mulenga M, Bailey JA, Chongwe G, Louis TA, Shapiro TA, Moss WJ; Southern and Central Africa International Centers of Excellence for Malaria Research. Whole Blood Transfusion for Severe Malarial Anemia in a High Plasmodium falciparum Transmission Setting. Clin Infect Dis. 2022 Nov 30;75(11):1893-1902. doi: 10.1093/cid/ciac304.