Whole Blood Transfusion for Malaria

(PLATFORM Trial)

Recruiting at 1 trial location

Overseen By Matthew M Ippolito, MD PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins Bloomberg School of Public Health

Disqualifiers: Foster care, Outside area, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

132 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of whole blood transfusion for malaria?

Research shows that platelets, a component of whole blood, can directly kill malaria parasites in the blood, suggesting that whole blood transfusions might help control malaria by reducing the number of parasites. ^{1 2 3 4 5}

Is whole blood transfusion generally safe for humans?

Whole blood transfusion is generally considered safe, but there can be risks such as infections from bacteria, viruses, or parasites. Adverse reactions can occur, and safety measures like pathogen reduction technology are used to minimize these risks. ^{6 7 8 9 10}

How does whole blood transfusion differ from other treatments for malaria?

Whole blood transfusion for malaria is unique because it involves transfusing all components of blood, including red blood cells, white blood cells, platelets, and plasma, which can help restore blood volume and improve oxygen delivery. This is different from other treatments that may focus on specific components or medications to target the malaria parasite directly. ^{3 9 11 12 13}

Research Team

Matthew M Ippolito, MD, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for children under 5 with severe malaria and low platelet count, living within a certain health clinic area. They must have a specific level of parasites in their blood and hemoglobin between certain values. Kids in foster care or planning to move out of the area can't join.

Inclusion Criteria

Platelet count ≤75,000/uL

I am under 5 years old.

Hemoglobin >5 and ≤9 g/dL

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive whole blood transfusion or standard-of-care treatment

Up to 28 days

In-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 days

Daily in-hospital assessments

Extension

Participants may be monitored for long-term outcomes post-discharge

Long-term

Treatment Details

Interventions

• Whole blood transfusion

Trial Overview The study is testing if giving whole blood transfusions to kids with severe malaria helps them survive better. It's an open-label trial, meaning everyone knows who gets the transfusion, and it randomly decides who gets treated.

Participant Groups

Group I: Whole blood transfusion Experimental Treatment 1 Intervention

Whole blood transfusion x1 (20 mL/kg)

Group II: Control Active Control 1 Intervention

Standard-of-care

Who Is Running the Clinical Trial?

Johns Hopkins Bloomberg School of Public Health

Lead Sponsor

Trials

441

Recruited

2,157,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Tropical Diseases Research Centre

Collaborator

Trials

3

Recruited

1,700+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Findings from Research

In a study of 639 dengue patients, prophylactic platelet transfusions did not significantly reduce minor bleeding episodes compared to those who did not receive transfusions, with 31.1% experiencing bleeding in the transfused group versus 13.7% in the non-transfused group.

The study also found that patients receiving transfusions had a higher mortality rate (1.9% vs. 0.2%) and incurred significantly higher hospital costs, suggesting that prophylactic transfusions may not be beneficial and could lead to increased healthcare expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of prophylactic platelet transfusion in patients with dengue: A retrospective study of patients at a tertiary care hospital in Karachi. Sethi, SM., Khalil, A., Naseem Khan, MR., et al.[2019]

In a study of 372 dengue patients with low platelet counts, poor platelet recovery was linked to older age, lower white cell counts, and earlier presentation during illness, indicating these factors can predict recovery outcomes.

Platelet transfusion did not improve recovery in patients with poor platelet counts and was associated with a higher risk of bleeding, suggesting that transfusions may not be beneficial and could be harmful in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study. Archuleta, S., Chia, PY., Wei, Y., et al.[2021]

In a study of 261 children with dengue fever, only 6.5% required platelet transfusions, primarily in cases of severe dengue with significant bleeding or very low platelet counts, highlighting the need for careful assessment before transfusion.

Bleeding manifestations in dengue do not always correlate with platelet counts, indicating that platelet transfusion should not be solely based on bleeding symptoms, especially since some children with normal platelet counts also experienced bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of platelet transfusion in children with bleeding in dengue fever. Pothapregada, S., Kamalakannan, B., Thulasingam, M.[2016]

In a study of 159 patients with malaria, thrombocytopenia (low platelet count) was found in 89.3% of cases, indicating that platelet parameters can be important indicators of disease severity in both Plasmodium falciparum and Plasmodium vivax infections.

A platelet count of 50,000 cell/mm3 and a plateletcrit of 0.05% were identified as potential markers for predicting severe malaria, with both showing moderate sensitivity and specificity, suggesting that monitoring these parameters could help in assessing the severity of malaria cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of platelet count and platelet indices and their potential role to predict severity in malaria. Gupta, P., Guddattu, V., Saravu, K.[2020]

In a study of 376 malaria patients, platelets were found to directly bind to and kill various stages of Plasmodium parasites, particularly in those infected with Plasmodium vivax, suggesting a significant role for platelets in the immune response against malaria.

The research indicated that platelet-associated parasite killing correlated inversely with patient parasite loads, implying that platelets may help control the growth of a substantial proportion of circulating malaria parasites, contributing to the understanding of malarial thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelets kill circulating parasites of all major Plasmodium species in human malaria. Kho, S., Barber, BE., Johar, E., et al.[2023]

Blood component transfusions are generally considered safe, but there is still a risk of adverse events, particularly infections from viruses, bacteria, and parasites.

Real-time polymerase chain reaction (PCR), specifically targeting 16S rDNA, is a promising method for detecting bacterial contamination in platelet concentrates, which is crucial for ensuring transfusion safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid screening by real-time 16S rDNA PCR for bacterial contamination of blood products. Reesink, HW., Mohammadi, T., Pietersz, RN., et al.[2016]

Apheresis platelets (APLTs) have a significantly higher rate of adverse reactions compared to whole blood-derived platelets (WBD-PLTs), with 478 vs 70 reactions per 100,000 transfusions, and APLTs are more likely to result in serious reactions (34 vs 6 per 100,000).

Pathogen reduction technology (PRT) in APLTs reduces the rate of serious adverse reactions, although the overall reaction rate remains higher than WBD-PLTs, highlighting the need for ongoing monitoring and safety measures in platelet transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of Transfusion-Related Adverse Reactions Among Apheresis Platelets, Whole Blood-Derived Platelets, and Platelets Subjected to Pathogen Reduction Technology as Reported to the National Healthcare Safety Network Hemovigilance Module. Mowla, SJ., Kracalik, IT., Sapiano, MRP., et al.[2021]

In a study involving 1068 transfusion-dependent hematology-oncology patients, pathogen-reduced platelet components (PRPC) were found to be non-inferior to conventional platelet components (CPC) in terms of the incidence of treatment-emergent assisted mechanical ventilation (TEAMV), with a lower rate of 2.9% compared to 4.6% for CPC.

PRPC also showed a significant reduction in allergic transfusion reactions compared to CPC, indicating a potential safety advantage, while maintaining similar rates of other adverse events and not increasing the need for additional blood products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components. Snyder, EL., Wheeler, AP., Refaai, M., et al.[2023]

Leukodepletion through filtration of platelet transfusions shows promise in reducing alloimmunization and the incidence of transfusion reactions, which are often caused by cytokines in the plasma.

Ongoing research, including the Trial to Reduce Alloimmunization to Platelets, aims to optimize strategies for minimizing side effects of transfusions, such as the transmission of infections and the risk of serious bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet transfusion support for patients with cancer and hematologic malignancies. Sarkodee-Adoo, C., Schiffer, CA.[2019]

Platelet concentrates, while accounting for 10% of blood components, are linked to over 25% of adverse events, highlighting the need for improved safety measures during collection and storage.

Research indicates that whole blood buffy coat pooled platelets are safer than apheresis platelets, showing lower risks of infections and inflammatory reactions, suggesting a need to reconsider current transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving platelet transfusion safety: biomedical and technical considerations. Garraud, O., Cognasse, F., Tissot, JD., et al.[2018]

The manual washing procedure for preparing washed platelet concentrates (W-PC) resulted in a platelet recovery rate of 84.8%, with only minor effects on platelet activation and function, indicating that the method is effective for maintaining platelet quality.

In a pilot study involving 11 onco-hematology patients, W-PC transfusions showed similar efficacy to standard platelet concentrates (S-PC) in terms of platelet count increments and did not lead to an increased risk of bleeding events, suggesting that W-PCs are a safe alternative for patients with previous allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality assessment and transfusion efficacy of buffy coat-derived platelet concentrates washed with platelet additive solution. Fernández-Muñoz, H., Castilla-Llorente, C., Plaza, EM., et al.[2019]

Single donor platelets (SDP) are considered to have significant advantages over platelet concentrates (PC) in treating patients with thrombocytopenia, particularly in reducing the risk of infectious complications and transfusion reactions.

The review highlights that SDP may lead to better patient outcomes by minimizing alloimmunization and reducing the frequency of transfusions needed for patients with bone marrow suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single donor versus pooled random donor platelet concentrates. Ness, PM., Campbell-Lee, SA.[2022]

In a study of 55 patients undergoing allogeneic hematopoietic cell transplantation, transfusions of buffy-coat platelet concentrates (BC-PCs) resulted in a significantly higher 24-hour corrected count increment (CCI) compared to platelet-rich plasma concentrates (PRP-PCs), indicating better efficacy in increasing platelet counts.

While BC-PCs reduced donor exposure (5.0 vs. 5.8 for PRP-PCs), there was no significant difference in bleeding events between the two groups, suggesting that while BC-PCs may be more effective in raising platelet levels, they do not necessarily lead to fewer bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of prophylactic transfusions of platelet concentrates obtained by the PRP or buffy-coat methods, in patients undergoing allogeneic hematopoietic stem cell transplantation. Fernández-Muñoz, H., Plaza, EM., Rivera-Caravaca, JM., et al.[2018]

References

1. Pakistan pubmed.ncbi.nlm.nih.gov

Clinical outcomes of prophylactic platelet transfusion in patients with dengue: A retrospective study of patients at a tertiary care hospital in Karachi. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study. [2021]

3. India pubmed.ncbi.nlm.nih.gov

Role of platelet transfusion in children with bleeding in dengue fever. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Characterization of platelet count and platelet indices and their potential role to predict severity in malaria. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Platelets kill circulating parasites of all major Plasmodium species in human malaria. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Rapid screening by real-time 16S rDNA PCR for bacterial contamination of blood products. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

A Comparison of Transfusion-Related Adverse Reactions Among Apheresis Platelets, Whole Blood-Derived Platelets, and Platelets Subjected to Pathogen Reduction Technology as Reported to the National Healthcare Safety Network Hemovigilance Module. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Platelet transfusion support for patients with cancer and hematologic malignancies. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

Improving platelet transfusion safety: biomedical and technical considerations. [2018]

11. Italy pubmed.ncbi.nlm.nih.gov

Quality assessment and transfusion efficacy of buffy coat-derived platelet concentrates washed with platelet additive solution. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Single donor versus pooled random donor platelet concentrates. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Comparative assessment of prophylactic transfusions of platelet concentrates obtained by the PRP or buffy-coat methods, in patients undergoing allogeneic hematopoietic stem cell transplantation. [2018]