Whole Blood Transfusion for Malaria
(PLATFORM Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Johns Hopkins Bloomberg School of Public Health
Disqualifiers: Foster care, Outside area, others
No Placebo Group
Approved in 1 Jurisdiction
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.
12345Is 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.
678910How 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.
39111213Eligibility 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
+5 more
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
+1 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Whole blood transfusionExperimental Treatment1 Intervention
Whole blood transfusion x1 (20 mL/kg)
Group II: ControlActive Control1 Intervention
Standard-of-care
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins Bloomberg School of Public HealthBaltimore, MD
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Who Is Running the Clinical Trial?
Johns Hopkins Bloomberg School of Public HealthLead Sponsor
Johns Hopkins UniversityCollaborator
Tropical Diseases Research CentreCollaborator
University of California, San FranciscoCollaborator
University of MarylandCollaborator
References
Clinical outcomes of prophylactic platelet transfusion in patients with dengue: A retrospective study of patients at a tertiary care hospital in Karachi. [2019]To determine the benefit of prophylactic platelet transfusion on clinical outcomes in patients with dengue fever.
Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study. [2021]Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants.
Role of platelet transfusion in children with bleeding in dengue fever. [2016]The indications for platelet transfusion in dengue fever are clearly defined in World Health Organization (WHO) guidelines (2011) for dengue fever, but physicians face practical difficulty in its implementation in an epidemic setting. On one hand there is an intense social pressure created by the panic-struck parents to transfuse platelets in presence of bleeding and on the other hand there is a need for its judicious use as the requirement is more than its availability. The study was aimed to assess the clinico-hematological parameters, and the requirement and need for platelet transfusion in children with dengue fever.
Characterization of platelet count and platelet indices and their potential role to predict severity in malaria. [2020]The association of hematological parameters especially platelet parameters with disease severity in malaria is poorly understood. We aimed to characterize the platelet parameters across Plasmodium falciparum and Plasmodium vivax malaria stratified by severity and to elucidate the potential role of platelet parameters to predict disease severity. Individuals > 18 years, of either gender with microscopically proven symptomatic malaria were prospectively enrolled between October 2014 and August 2016 in a tertiary center in Manipal, India. Severity of malaria was defined as per the WHO definition. Among 159 patients, 32 (20.1%) had severe malaria. 116 (73%) had infection with P. vivax, 37 (23%) P. falciparum and 6 mixed infection. Thrombocytopenia was seen in 32 (86.4%) of P. falciparum and 105 (90.5%) of P. vivax malaria cases. Patients with renal failure (p=0.02), shock (p=0.04) and liver dysfunction (p<0.001) had significantly lower platelet count compared to those who did not. Admission platelet count of 50,000 cell/mm3 had a sensitivity and specificity of 65.6% and 70.6% respectively, to discriminate severe malaria. A plateletcrit of 0.05% had a sensitivity and specificity of 65.6 % and of 70.6% respectively. Thrombocytopenia was seen in 89.3% of malaria cases due to both P. vivax and P. falciparum. Platelet count and plateletcrit could be used as markers of disease severity. P. vivax malaria which has been traditionally regarded as 'benign' can be as sinister and menacing as P. falciparum malaria and hence warrants equal attention. Unnecessary transfusion of platelets should be avoided.
Platelets kill circulating parasites of all major Plasmodium species in human malaria. [2023]Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the Plasmodium species studied, particularly mature stages, and was greatest in P vivax patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4+TUNEL+ parasites). These PF4+TUNEL+ parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and Plasmodium species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet-erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in P knowlesi culture. Collectively, our results indicate that platelets directly contribute to innate control of Plasmodium infection in human malaria.
Rapid screening by real-time 16S rDNA PCR for bacterial contamination of blood products. [2016]Although blood component transfusion is currently regarded as safe, adverse events may occur in recipients of these products. Among those, blood borne viral, bacterial and parasitic infections are best known. For detection of bacterial contamination in platelet concentrates various methods are available or under investigation. One of these methods, real-time polymerase chain reaction (PCR) with particular focus on real-time 16S rDNA detection, will be discussed in this review.
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]Despite advances in transfusion safety, concerns with safety of platelet transfusions remain including platelet-related sepsis and higher reaction rates observed among patients receiving apheresis platelets (APLTs). National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) data were analyzed to quantify the burden and severity of adverse reactions occurring from APLTs and whole blood-derived platelets (WBD-PLTs). Facilities participating in NHSN HM during 2010-2018 were included. Adverse reaction rates (number per 100,000 components transfused) were calculated for APLTs and WBD-PLTs stratified by severity, use of platelet additive solution (PAS), and pathogen reduction technology (PRT). Chi-square tests were used to compare rates. During the study interval, 2,000,589 platelets were transfused: 1,435,154 APLTs; 525,902 WBD-PLTs; and among APLTs, 39,533 PRT-APLTs. APLT adverse reaction rates were higher (478 vs 70/ 100,000, P
Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components. [2023]Platelet transfusion carries risk of transfusion-transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion-related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion.
Platelet transfusion support for patients with cancer and hematologic malignancies. [2019]Advances in platelet transfusion have contributed to improved outcomes in the treatment of patients with cancer and leukemia. However, the optimal strategies to avoid some of the side effects that could result from platelet transfusions remain under investigation. These side effects include the development of refractoriness to transfusions, alloimmunization, transfusion reactions, the transmission of infectious agents, and transfusion-associated graft-versus-host disease. Leukodepletion by filtration is promising as a means of preventing the development of alloimmunization. Results of the Trial to Reduce Alloimmunization to Platelets will be reported shortly and will shed more light on that issue. Bedside filtration of cellular blood products also diminishes the transmission of cytomegalovirus infections by that route. Transfusion reactions are often mediated by cytokines in the plasma fraction of transfused platelet concentrates, and leukodepletion prior to storage reduces their incidence. Serious bacterial infections are sometimes transmitted by platelet transfusions and improved methods are needed for their detection and prevention. Photochemical methods that could inactivate bacteria and viruses in contaminated products deserve further study.
Improving platelet transfusion safety: biomedical and technical considerations. [2018]Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards.
Quality assessment and transfusion efficacy of buffy coat-derived platelet concentrates washed with platelet additive solution. [2019]Transfusion of washed platelet concentrates (W-PC) is recommended for some patients, such as those who have had previous severe allergic transfusion reactions. However, we still lack a standardised method for preparing these products. Here, we assessed the effect of a manual washing procedure on in vitro platelet quality and on the transfusion efficacy of W-PCs.
Single donor versus pooled random donor platelet concentrates. [2022]Both platelet concentrates (PC) derived from whole blood or single donor platelets (SDP) obtained from a single donor by apheresis are indicated to treat acute hemorrhage secondary to thrombocytopenia or to provide prophylaxis from hemorrhage in patients with bone marrow aplasia. Currently platelet transfusion therapy is limited by several concerns, including the consequences of alloimmunization in chronically transfused patients and septic reactions caused by bacterial contamination. There is debate about which platelet product should be used; many transfusion services favor the primary use of PC, whereas others favor SDP. This review will discuss five areas that should be considered when considering the use of SDP or PC: (1) the impact on infectious complications, (2) transfusion reaction rate, (3) leukodepletion, (4) reduction of transfusion frequency in patients with bone marrow suppression and, (5) the treatment and prevention of alloimmunization. The authors believe that SDP offers major advantages over PC for most of these issues, particularly when improved patient care is given primary emphasis.
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]Whole blood-derived platelet concentrates can be obtained by the platelet-rich plasma (PRP-PCs) or the buffy-coat (BC-PCs) method. Few studies have shown that BC-PCs display lower in vitro platelet activation, but scarce information exists regarding transfusion efficacy. We have performed a retrospective study assessing platelet transfusion in patients undergoing allogeneic hematopoietic cell transplantation (AHCT) in our clinic, before and after the implementation of BC-PCs.