Platelet-Directed Whole Blood Transfusion Strategy for Malaria

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical and Translational Investigations of Severe Malaria Pathophysiology [Parent Study Protocol]

Conditions
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Severe Malaria, Thrombocytopenia

Intervention / Treatment
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* Other: Whole blood transfusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole blood transfusion<br>Whole blood transfusion x1 (20 mL/kg) | Other: Whole blood transfusion<br>* Whole blood is sourced from the Zambia National Blood Transfusion Service.<br>|
| No Intervention: Control<br>Standard-of-care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of all-cause mortality | Death due to any cause | Up to hospital discharge or in-hospital death, up to 28 days on average | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin (Hb) | The difference in Hb concentration between baseline (pre-transfusion) and post-transfusion | 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 | 
| Change in platelet count | The difference in the platelet count between baseline (pre-transfusion) and post-transfusion | 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 | 
| Change in white blood cell (WBC) count | The difference in the WBC count between baseline (pre-transfusion) and post-transfusion | 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 | 
| Incidence of transfusion reaction | Transfusion reactions (e.g., hypersensitivity, TACO, TRALI) graded on severity and likeliness of being related to transfusion | During or after transfusion, up to the day of hospital discharge or in-hospital death, up to 28 days on average | 
| Length of hospitalization | Interval in days from date of admission to date of discharge/death | Up to hospital discharge or in-hospital death, up to 28 days on average | 
| Parasite clearance | Time to microscopic conversion to negative | 0-72 hours, measured every 12±2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Plasmodium falciparum, Zambia