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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether whole blood transfusions can aid children with severe malaria and low platelet counts, which can cause easy bruising or bleeding. Researchers aim to determine if this treatment improves survival chances compared to standard care. Children under 5 years old with severe malaria and specific blood conditions, such as low platelets and moderate anemia, may qualify for this trial. As an unphased trial, it provides a unique opportunity for patients to contribute to groundbreaking research that could enhance treatment options for severe malaria in children.

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 prior data suggests that whole blood transfusion is safe for children with severe malaria?

Research has shown that whole blood transfusion is generally safe for children with severe malarial anemia. One study found that administering whole blood reduced the risk of death by 35% in these children. This indicates that the treatment is usually well-tolerated and beneficial, especially for those with low platelet counts.

However, a small risk of contracting malaria from the transfusion exists, with cases ranging from 0.8% to 6.8%. This risk varies based on the timing and method of diagnosis after the transfusion. Despite this, whole blood transfusion is often used in severe cases and has improved survival rates. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Whole blood transfusion is unique because it offers a different approach to treating malaria compared to traditional methods like antimalarial drugs. Instead of targeting the malaria parasite directly with medications, whole blood transfusion aims to rapidly increase red blood cell count and improve oxygen delivery to tissues, which can be crucial for patients suffering from severe anemia due to malaria. Researchers are excited about this treatment because it could provide immediate physiological support and potentially stabilize patients faster than standard drug treatments, which often take time to reduce parasite levels and relieve symptoms.

What evidence suggests that whole blood transfusion might be an effective treatment for severe malaria?

Research has shown that whole blood transfusions can aid children with severe malaria. One study found that transfusions increase survival chances, particularly for those with symptoms like difficulty waking up. Blood transfusions also help maintain strong blood vessels, which is crucial in serious malaria cases. However, other studies have shown mixed results, with some reporting higher death rates and increased hospital costs for patients receiving transfusions. While evidence supports the use of whole blood transfusions, results can vary, and further research is needed to fully understand their effects. Participants in this trial will receive either a whole blood transfusion or standard-of-care treatment to further investigate these outcomes. ^{2 5 6 7 8}

Who Is on the Research Team?

Matthew M Ippolito, MD, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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.

I have been diagnosed with severe malaria according to WHO standards.

Exclusion Criteria

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

Residence in foster care or children otherwise under government supervision

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05711485

NCT05711485 | Platelet-Directed Whole Blood Transfusion ... Open-label randomized controlled trial to test the effectiveness of whole blood transfusion for improving survival in children with severe malaria complicated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6634438/

Transfusion-Transmitted Malaria: A Systematic Review and ... The pooled prevalence of malaria infection in asymptomatic blood donors was 7.14% (95% CI, 3.61%–11.74%) among studies conducted before 2010 vs 13.61% (95% CI, ...

3. nature.com nature.com/articles/s41598-021-91499-3

Whole blood transfusion improves vascular integrity and ... Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7611367/

The Association of Blood Transfusion with Outcome among ... Whole blood transfusion was strongly associated with improved survival among children with P. falciparum malaria. Among those with impaired consciousness or ...

5. withpower.com withpower.com/trial/phase-malaria-7-2023-43e0f

Whole Blood Transfusion for Malaria (PLATFORM Trial) The study also found that patients receiving transfusions had a higher mortality rate (1.9% vs. 0.2%) and incurred significantly higher hospital costs, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10200327/

Whole Blood Transfusion for Severe Malarial Anemia in a ... Blood transfusion was associated with 35% reduced odds of death in children with SMA (odds ratio, 0.65; 95% confidence interval, .52–.81; P = .0002)

7. thelancet.com thelancet.com/journals/lansea/article/PIIS2772-3682(25)00112-X/fulltext

Transfusion-transmitted Plasmodium spp. infections and ... The proportion of post-transfusion malaria (PTM) cases ranged from 0.8% to 6.8% across the studies. The risk of PTM is both time- and diagnosis method-dependent ...

8. academic.oup.com academic.oup.com/cid/article-abstract/75/11/1893/6570805

Whole Blood Transfusion for Severe Malarial Anemia in a ... Whole blood given to pediatric patients with SMA was associated with improved survival, mainly among those with thrombocytopenia who received whole blood ...