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Pathogen Reduction Evaluation & Predictive Analytical Rating Score (PREPAReS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02783313
Recruitment Status : Completed
First Posted : May 26, 2016
Last Update Posted : August 23, 2018
Sponsor:
Collaborator:
Terumo BCT
Information provided by (Responsible Party):
Sanquin Research & Blood Bank Divisions

Tracking Information
First Submitted Date  ICMJE April 11, 2016
First Posted Date  ICMJE May 26, 2016
Last Update Posted Date August 23, 2018
Study Start Date  ICMJE November 17, 2010
Actual Primary Completion Date April 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
Percentage of patients with WHO grade ≥ 2 bleeding complications [ Time Frame: Transfusion episode (from the day of the first on-study transfusion until study completion), an average of 20 days ]
Any WHO grade ≥ 2 bleeding event, as determined by daily assessment of bleeding symptoms, and documentation of any red blood cell transfusions to treat bleeding
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
  • 1 and 24 hour count increment [ Time Frame: 1 and 24 hours post-transfusion ]
  • 1 and 24 hour corrected count increment (CCI) [ Time Frame: 1 and 24 hours post-transfusion ]
  • (1+24 hour CCI)/2 [ Time Frame: 1 and 24 hours post-transfusion ]
  • Adverse transfusion reactions [ Time Frame: On-study episode (from the day of randomization until study completion), an average of 25 days ]
    All transfusion-associated side effects observed within 6 hours after platelet transfusion
  • Total transfusion requirement of red cells and platelets [ Time Frame: Transfusion episode (from the day of the first on-study transfusion until study completion), an average of 20 days ]
    Number of occurrences of a platelet transfusion or a red cell transfusion among subjects who have had at least one platelet transfusion
  • Platelet transfusion interval [ Time Frame: Transfusion episode (from the day of the first on-study transfusion until study completion), an average of 20 days ]
    Time in hours between the last and first occurrence of a platelet transfusion, divided by the number of platelet transfusion occurrences minus 1, among subjects who have had at least two platelet transfusions
  • Rate of HLA allo-immunization [ Time Frame: From the day of randomization until 56 days after randomization ]
  • In vitro quality markers related with the 1-hour or 24-hour CCI [ Time Frame: 1 and 24 hours post-transfusion ]
  • Clinical factors interacting on primary endpoint, including in vivo variables of immunological responses; and of hemostasis in the recipients after transfusion as compared prior to transfusion. [ Time Frame: Transfusion episode (from the day of the first on-study transfusion until study completion), an average of 20 days ]
    Severity of the WHO bleeding grade as determined by daily assessment of bleeding symptoms, related to the level of circulating HLA allo antibodies as determined in a blood sample collected every week during the on-study episode; severity of the WHO bleeding grade as determined by daily assessment of bleeding symptoms at the day of occurrence of a platelet transfusion as compared to the day after the occurrence of a platelet transfusion
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pathogen Reduction Evaluation & Predictive Analytical Rating Score
Official Title  ICMJE Clinical Effectiveness of Standard Versus Pathogen-reduced Buffy Coat-derived Platelet Concentrates in Plasma in Hemato-oncological Patients.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Thrombocytopenia
Intervention  ICMJE
  • Device: Pathogen reduced plasma-stored platelet concentrates
    Platelet concentrates treated with the Mirasol PRT system (pathogen reduction technology) and stored in plasma.
  • Other: Plasma-stored platelet concentrates
    Platelet concentrates stored in plasma
Study Arms  ICMJE
  • Experimental: PR-plasma-PCs
    Pooled buffy coat-derived pathogen reduced plasma-stored platelet concentrates (PR-plasma-PCs)
    Intervention: Device: Pathogen reduced plasma-stored platelet concentrates
  • Active Comparator: Plasma-PCs
    Pooled buffy coat-derived plasma-stored platelet concentrates (plasma-PCs)
    Intervention: Other: Plasma-stored platelet concentrates
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2017)
567
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 30, 2016
Actual Primary Completion Date April 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Netherlands,   Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02783313
Other Study ID Numbers  ICMJE ABR30643
NTR2106 ( Registry Identifier: Dutch Trial Register )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Sanquin Research & Blood Bank Divisions
Study Sponsor  ICMJE Sanquin Research & Blood Bank Divisions
Collaborators  ICMJE Terumo BCT
Investigators  ICMJE
Principal Investigator: Jean-Louis Kerkhoffs, MD, PhD Sanquin Blood Bank
PRS Account Sanquin Research & Blood Bank Divisions
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP