Pathogen Reduction Evaluation & Predictive Analytical Rating Score

NCT ID: NCT02783313

Last Updated: 2018-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 567 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-17
• Study Completion Date: 2016-06-30

Brief Summary

The objective of this study is to determine if pooled buffy coat-derived pathogen reduced plasma-stored platelet concentrates are non-inferior compared to plasma-stored platelet concentrates in terms of WHO bleeding complications in hemato-oncological patients with thrombocytopenia.

Detailed Description

Currently some pathogen-reduced platelet products (PR-PCs) have passed phase III studies, are in progress or can be expected in the near future. At present some transfusion centers throughout Europe have implemented PR-PCs, but as yet PR-PCs are not formally accepted as a standard product that should be applied nation-wide. Because many uncertainties currently exist on the "optimal" platelet product, it is in the interest of patients, health care providers and the transfusion provider (Sanquin) to decide on evidence.

With all the current safety measures remaining in place, pathogen reduction provides a safety benefit by reducing the number of transfusions of platelet concentrates contaminated with bacteria, but which were missed by the screening method. In the Dutch situation, morbidity is estimated to be 1:14,000 platelet concentrates [Te Boekhorst, Transfusion 2005]. In this publication, two cases of transmission of B. cereus by a platelet transfusion are reported, where both patients experience a life-threatening sepsis, but recover eventually. Cases of bacterial transmission however often go unnoted, so a frequency as low as 1:130,000 has been reported [Dumont, Transfusion 2010]. The same is true for mortality; this value ranges from 1:50,000 to 1:500,000.

A more precautionary benefit is protection against known and unknown pathogens. It is difficult to estimate the actual risk, and consequently to estimate the benefit for the patient. While in The Netherlands no epidemics have occurred against which no screening tests could be developed, including Q-fever, there is a small but real risk that an epidemic can wipe out the blood supply in a country. This has happened in La Réunion, where an epidemic of chikungunya virus urged import of blood products from abroad, followed by rapid introduction of a pathogen reduction technology to ensure the blood supply [Rasongles, Transfusion 2009]. An outbreak of this virus in Italy resulted in suspension of blood collections in an affected area, which led to a low blood inventory as well as a reduced delivery of plasma to fractionation institutes.

Appreciating the difficulties of extrapolating in vitro tests towards in vivo efficacy, platelet products should be tested in clinical trials. Of note, radiolabeling techniques in volunteers as required by the FDA, are not used in the Netherlands. For major product variations in the Netherlands, investigators depend on studies in patients. Extending storage for logistic purposes, combined with maintaining or even improving the safety of platelet products, and maintaining clinical efficacy are the main features in the development of new platelet products. In this study protocol, the aim is to investigate transfusion efficacy of two different platelet products: plasma-PCs, and pathogen-reduced (PR)-plasma-PCs, combining extended storage with or without treatment with a photochemical pathogen reduction technique. Prior to the start of the clinical study an in vitro study of the product has been performed, showing that the study product meets the current in vitro quality requirements for release for transfusion. However, on site implementation validation still has to take place.

Refractoriness to platelet transfusions and bleeding complications are the main clinical problems in intensively treated hemato-oncological patients and are essential endpoints for transfusion studies as well. In this trial, bleeding will be scored according to the World Health Organization (WHO) scale as a primary endpoint. Refractoriness is defined as a 1-hour CCI <7.5 and/or a 24-hour CCI <4.5 after ABO compatible platelet transfusions on at least two successive occasions. Known causes of non-alloimmune refractoriness are included in this trial because for the purpose of generalization, relevant to develop a national product, testing transfusion efficacy of new platelet products should imply all patients in need of a preventive support with platelet transfusions. The 1- and 24-hour CCI are commonly used to evaluate platelet transfusions and, albeit not without discussion, currently the platelet count is the only parameter in trigger-based transfusion policy. The ratio of both the 1-hour and 24-hour CCI mirrors both platelet recovery immediately after transfusion as the 1-hour CCI, and platelet survival one day after transfusion as the 24-hour CCI. Other secondary clinical endpoints of the trial will be transfusion requirement (red cells and platelets), transfusion interval to next transfusion and adverse reactions.

Conditions

Thrombocytopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

PR-plasma-PCs

Pooled buffy coat-derived pathogen reduced plasma-stored platelet concentrates (PR-plasma-PCs)

Group Type: EXPERIMENTAL

Pathogen reduced plasma-stored platelet concentrates

Intervention Type: DEVICE

Platelet concentrates treated with the Mirasol PRT system (pathogen reduction technology) and stored in plasma.

Plasma-PCs

Pooled buffy coat-derived plasma-stored platelet concentrates (plasma-PCs)

Group Type: ACTIVE_COMPARATOR

Plasma-stored platelet concentrates

Intervention Type: OTHER

Platelet concentrates stored in plasma

Interventions

Pathogen reduced plasma-stored platelet concentrates

Platelet concentrates treated with the Mirasol PRT system (pathogen reduction technology) and stored in plasma.

Intervention Type: DEVICE

Plasma-stored platelet concentrates

Platelet concentrates stored in plasma

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years;

2. Expected ≥ 2 platelet transfusion requirements;

3. Signed informed consent;

4. Having hemato oncological disease including those who undergo myelo ablative allogeneic stem cell transplant therapy.

Exclusion Criteria

1. Micro-angiopathic thrombocytopenia (TTP, HUS) and ITP;

2. Bleeding > grade 2 at randomization ( after treatment, the patient can be randomized in the study after 2 or more weeks after the last transfusion that was used to stop the bleeding);

3. Known immunological refractoriness to platelet transfusions;

4. HLA- and/or HPA-allo immunization and/or clinical relevant auto-antibodies;

5. Indications to use hyper-concentrated (plasma-reduced) platelet concentrates, i.e. patients with known severe allergic reactions and documented transfusion-associated circulatory overload (TACO);

6. Pregnancy (or lactating);

7. Prior treatment with pathogen-reduced blood products;

8. Known allergy to riboflavin or its photoactive products.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Terumo BCT

INDUSTRY

Sponsor Role: collaborator

Sanquin Research & Blood Bank Divisions

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Louis Kerkhoffs, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sanquin Blood Bank

Locations

McMaster University

Hamilton, , Canada

Kingston General Hospital

Kingston, , Canada

London Health Sciences Centre

London, , Canada

Ottawa Hospital

Ottawa, , Canada

Sunnybrook Health Sciences Centre

Toronto, , Canada

Leiden University Medical Center

Leiden, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Haga Ziekenhuis

The Hague, , Netherlands

Haukeland University Hospital

Bergen, , Norway

Countries

Canada; Netherlands; Norway

References

Ypma PF, van der Meer PF, Heddle NM, van Hilten JA, Stijnen T, Middelburg RA, Hervig T, van der Bom JG, Brand A, Kerkhoffs JL; PREPAReS Study Group. A study protocol for a randomised controlled trial evaluating clinical effects of platelet transfusion products: the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial. BMJ Open. 2016 Jan 27;6(1):e010156. doi: 10.1136/bmjopen-2015-010156.

Reference Type: BACKGROUND

PMID: 26817642 (View on PubMed)

van der Meer PF, Ypma PF, van Geloven N, van Hilten JA, van Wordragen-Vlaswinkel RJ, Eissen O, Zwaginga JJ, Trus M, Beckers EAM, Te Boekhorst P, Tinmouth A, Lin Y, Hsia C, Lee D, Norris PJ, Goodrich RP, Brand A, Hervig T, Heddle NM, van der Bom JG, Kerkhoffs JH. Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial. Blood. 2018 Jul 12;132(2):223-231. doi: 10.1182/blood-2018-02-831289. Epub 2018 May 17.

Reference Type: RESULT

PMID: 29773572 (View on PubMed)

Other Identifiers

NTR2106

Identifier Type: REGISTRY

Identifier Source: secondary_id

ABR30643

Identifier Type: -

Identifier Source: org_study_id