Platelet Transfusion
Conditions
Brief summary
* Overall objective: to accumulate further experience with the use of pathogen-reduced platelet concentrates throughout the entire process chain from manufacture to clinical use of pathogen-reduced platelet concentrates and their efficacy and safety under real-world conditions. The study aims to better understand the impact of pathogen inactivation on the various steps of the overall supply chain in routine practice, whereby safety, measured in terms of the frequency of serious transfusion reactions and the type, imputability, and outcome of the reactions, is the primary endpoint. * Study product: Pathogen-reduced platelet concentrates. * Methodology: multi-center, open-label, prospective, non-interventional safety study.
Detailed description
The safety of blood products has significantly improved over the past 30 years due to enhanced donor selection and more sensitive testing for infectious agents. Nevertheless, a residual risk remains, particularly the risk of bacterial contamination in platelet concentrates. To mitigate this, pathogen reduction methods and/or bacterial detection tests can be employed. In Germany, there is currently limited large-scale experience under real-world conditions regarding how pathogen reduction of platelet concentrates (PC) affects the various stages of the process chain from production, distribution through to the clinical application and its impact on safety and efficacy.To better understand the effects, the non-interventional post-authorization safety study INITIATE evaluates various aspects of pathogen-reduced, platelet concentrates across the entire process chain and compares results to historical data of standard, non-pathogen reduced PC. This project is a multi-center, open-label, prospective, non-interventional post-authorisation safety-study and is divided into two parts: Part 1 focuses on product- and process-related objectives. It includes all pathogen-reduced PC units produced at participating manufacturing sites to analyse the product and supply-related endpoints including manufacturing data, quality control data, logistics and supply, safety and costs. Part 1 shall include data on 20.000 PC. Part 2 includes a defined number of patients requiring PC transfusions at participating clinical study centers. It aims to collect data on safety (primary and co-primary endpoint: transfusion reactions (frequency, type, severity, imputability and outcome, according to CTCAE) and efficacy (bleeding, platelet increment (subgroup of patients), alloimmunization or platelet refractoriness). Part 2 shall include 850 patients (with an expected total number of 4.500 to 5.000 PC transfusions).
Interventions
BIOLOGICALPathogen-Reduced Platelet Concentrates
Pathogen-reduced platelet concentrates which were either produced from 4, 5 or 8 buffy coats from whole blood donations or which were collected by apheresis.
Sponsors
Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years * Patients who, based on clinical indications\*, receive at least one platelet transfusion with a pathogen-reduced platelet concentrate for treatment of bleeding risk caused by severe thrombocytopenia resulting from impaired platelet production. (\* Taking into account the Cross-sectional Guidelines on the transfusion of blood components and plasma derivatives issued by the German Medical Association (Bundesärztekammer) in its current version.)
Exclusion criteria
Patients will not be included if they fulfil at least one of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of serious transfusion reactions after transfusion of pathogen-reduced platelet concentrates | Within 24 hours (acute) and up to 6 weeks (delayed) depending on transfusion reaction |
| Type, imputability and outcome of serious adverse reactions after transfusion of pathogen-reduced platelet concentrates. | Within 24 hours (acute) and up to 6 weeks (delayed) depending on transfusion reaction |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of severe bleeding events | Within 24 hours after platelet transfusion | Number of severe bleeding events per patient |
| Frequency of severe bleeding events | Within 24 hours after platelet transfusion | Proportion of patients with at least one severe bleeding event |
| Clinical outcome of severe bleeding events | Through study completion, up to 18 months | Outcome categorized as resolved, ongoing, or fatal |
| Daily number of pathogen-reduced platelet concentrates manufactured | Through study completion, up to 18 months | Number of pathogen-reduced platelet concentrates manufactured per day |
| Manufacturing Workload for Pathogen-Reduced Platelet Concentrates | Through study completion, up to 18 months | Cumulative hands-on manufacturing time per product |
| Manufacturing duration of pathogen-reduced platelet concentrates | Through study completion, up to 18 months | Time from start to completion of manufacturing |
| Manufacturing failure rate | through study completion, up to 18 months | Number and proportion of manufacturing failures |
| Availability of platelet concentrates for supply | Through study completion, up to 18 months | Number of released platelet concentrates available for distribution |
| Time from product release to distribution | Through study completion, up to 18 months | Time from release of platelet concentrates to transfer to the distribution department |
| Shelf-life extension of non-pathogen-reduced platelet concentrates | Through study completion, up to 18 months | Number of non-pathogen-inactivated platelet concentrates requiring shelf-life extension |
| Discard rate of platelet concentrates | Through study completion, up to 18 months | Number of platelet concentrates discarded |
| Platelet content of pathogen-reduced platelet concentrates | Through study completion, up to 18 months | Platelet content per pathogen-reduced platelet concentrate |
| Bacterial contamination of pathogen-reduced platelet concentrates | Through study completion, up to 18 months | Presence or absence of baterial contamination per platelet concentrates as determined by routine quality control testing |
| pH of pathogen-reduced platelet concentrats at end of sheld life | Through study completion, up to 18 months | pH value measured at the end of shelf life |
| Residual leukocyte count | Through study completion, up to 18 months | Residual leukocyte count per platelet concentrate |
| Out-of-Specification platelet concentrates | Through study completion, up to 18 months | Proportion of platelet concentrates outside of predefined quality specifications |
| Transfusion reactions | Within 24 hours (acute) and up to 6 weeks (delayed) depending on transfusion reaction | Number of acute and delayed transfusion reactions |
| HLA Alloimmunisation | Through study completion, up to 18 months | Incidence of newly detected HLA antibodies |
| Composite thrombelastographhy coagulation index | at least one measurement between 10 minutes and 24 hours post transfusion | Composite index derived from predefined thrombelastography parameters |
| Fibrinogen concentration | at least one measurement between 10 minutes and 24 hours post transfusion | Change in fibrinogen concentration after platelet transfusion |
| Time to next platelet concentrate transfusion under routine conditions | From completion of first transfusion until the next transfusion under routine clinical practice, assessed up to 18 months | Time interval to subsequent platelet transfusion |
| Number of platelet concentrates per patient | through study completion, up to 18 months | Total number of platelet transfusions per patients |
| Number of Red Blood Cell Transfusions per patient | Through study completion, up to 18 months | Total number of packed red blood cell transfusions per patient. |
| Number of Plasma Transfusions per patient | Through study completion, up to 18 months | Total number of plasma transfusions per patient |
| Cost of Platelet Concentrate products | through study completion, up to 18 months | Direct costs of platelet concentrate products |
| Reimbursement of platelet concentrates within the DRG System | Through study completion, up to 18 months | Reimbursement of platelet concentrates by health insurance providers |
| Cause of death | From date of enrollment until date of death from any cause, assessed up to 18 months. | Categorized cause of death |
| User satisfaction at the various stages of production, distribution and application of platelet concentrates | Through study completion, up to 18 months | User satisfaction at the various stages of production, distribution and application of platelet concentrates, measured on a scale of 0 to 10, with 10 representing best result, based on questionnaires at the start of the observational study, after three and six months and at the end of the study. |
| Overall survival | From date of enrollment until date of death from any cause, assessed up to 18 months | Time-to-event analysis of overall survival |
Countries
Germany
Contacts
CONTACTSimone Hoffmann, Dr. rer. nat.
STUDY_DIRECTORHubert Schrezenmeier, Prof. Dr. med.
Institut für Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH (DRK-Blutspendedienst Baden-Württemberg Hessen gGmbH und Universitätsklinikum Ulm AöR). Institut für Transfusionsmedizin, Universität Ulm
Outcome results
None listed