Back to results

Study on the Safety and Efficacy of Cryopreserved Platelets in Hypoproliferative Thrombocytopenic Patients

Primary Purpose

Hypoproliferative Thrombocytopenia

Status

Completed

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

Control arm receiving normal (never before frozen) platelets as per current clinical practice

Treatment arm receiving cryopreserved platelets

About this trial

This is an interventional treatment trial for Hypoproliferative Thrombocytopenia focused on measuring Hypoproliferative thrombocytopenia, Cryopreserved, Transfusion, Platelets, Safety, Efficacy

Eligibility Criteria

21 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 21 years of age
Be able to provide written informed consent
Current or potential hypoproliferative thrombocytopenia with expected platelet count of <20 X 109/L for a minimum of 5 days in a 28-day period
If pre-menopausal female of child bearing potential, then the subject must have a negative serum pregnancy test prior to study commencement, and must be using an acceptable method of contraception during the study.
Calculated creatinine clearance of >30 ml/min (as calculated based on the Cockcroft-Gault equation; National Kidney Foundation 2017) at the point of recruitment, and within one week before transfusion

Exclusion Criteria:

Not meeting the inclusion criteria specified above
Pregnant
Breastfeeding
Current platelet refractoriness
History of allergy or adverse reaction to DMSO
History of veno-occlusive disease
History of acute venous or arterial thromboembolism within the last 3 months.
History of unprovoked venous thromboembolism
On antiplatelets, NSAIDs or anticoagulants within 1 week, and TCM (traditional Chinese medicine) which are known to decrease platelet count or platelet function or increase bleeding tendency within 2 weeks of study enrolment.
Received or will be receiving L-asparaginase chemotherapy within 7 days of platelet transfusion
Renal impairment with calculated creatinine clearance of <30ml/min.
Non-cutaneous Grade 2 and above bleeding at the time of study assessment
Presently with or a history of acute promyelocytic leukemia (APML), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), haemolytic-uremic syndrome (HUS), or any thrombotic microangiopathy (TMA)
Presently with or a history of heparin-induced thrombocytopenia
Presently with disseminated intravascular coagulation (DIC) or other risk factor(s) for bleeding other than thrombocytopenia (including platelet dysfunction, PT ≥ 1.3 X upper limit of normal for the laboratory, PTT ≥ 1.3 X upper limit of normal for the laboratory, or fibrinogen ≤ 1 g/L)
History of anaphylaxis from blood transfusion
Involved in any other therapeutic clinical trials in the last 6 months prior to the start of this research
Concomitant participation in other therapeutic clinical trials during the full period of this study
Receiving non-trial-related medication that might compromise transfusion safety
Known history of congenital bleeding disorder
Subject who declined to consent for platelet transfusion

Sites / Locations

Singapore General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control arm

Treatment arm

Arm Description

Subjects in the "control" arm will receive normal pooled platelets for all of their transfusion within a single thrombocytopenic period. If subjects participate in the study for more than one thrombocytopenic period, they will automatically be enrolled in the opposing arm for their second thrombocytopenic period.

Subjects in the "treatment" arm will receive thawed cryopreserved pooled platelets for all of their transfusions (except for unplanned or urgent platelet transfusions outside stipulated periods when thawed cryopreserved platelets are unavailable) within a single thrombocytopenic period. If subjects participate in the study for more than one thrombocytopenic period, they will automatically be enrolled in the opposing arm for their second thrombocytopenic period.

Outcomes

Primary Outcome Measures

Incidence of adverse events related to platelet transfusion.

There would be a close visual observation of the patient throughout the transfusion for the earliest signs of a transfusion reaction. Because patients can experience transfusion reactions several hours after the transfusion is completed, inpatients should be observed for late reactions during the subsequent 24 hour. Outpatient patients and their carer would be counselled about the possibility of the late adverse reactions and given access to immediate clinical help if they develop any symptoms of a transfusion reaction within 24 hour post-transfusion. Patients receiving cryopreserved platelets will be monitored and assessed for the side-effects of DMSO within 24 hour. These side effects include: headache, nausea, sedation, dizziness, abdominal or chest & abdominal discomfort during and after transfusion. It also includes assessment for renal impairment related to DMSO by performing serum renal panel 18 to 30 hours post-transfusion of study platelets.

Non-cutaneous Grade 2 or higher bleeding (as defined on the WHO bleeding scale)

Patients will be monitored daily for bleeding during each thrombocytopenic period if they are inpatients. If they are outpatients, they will be reviewed for bleeding at each clinic visit, and they will be asked to keep a record of any bleeding symptoms which will also be reviewed at each clinical visit during each of the thrombocytopenic periods.

Secondary Outcome Measures

Platelet count increase (absolute increase and corrected count increment) post-platelet trantrsfusion

A pre-transfusion (baseline) venous blood sample for FBC will be taken by a trained phlebotomist/ nurse using Vacutainer tubes from the subject approximately within 24 hours prior to the planned platelet transfusion (for both "control" and "treatment" arms). Post-transfusion venous blood sample for FBC will be taken by a trained phlebotomist or nurse using Vacutainer tubes form the subject at 1-4 hour and 18-30 hour after transfusion.

Changes in platelet activity (measured by viscoelastic hemostatic assay) post-platelet transfusion

A pre-transfusion (baseline) venous blood sample for VHA (viscoelastic hemostatic assay) will be taken by a trained phlebotomist/ nurse using Vacutainer tubes from the subject approximately within 24 hours prior to the planned platelet transfusion (for both "control" and "treatment" arms). Post-transfusion venous blood sample for VHA will be taken by a trained phlebotomist or nurse using Vacutainer tubes form the subject at 1-4 hour and 18-30 hour after transfusion.

Changes in procoagulant activity post-platelet transfusion

A pre-transfusion (baseline) venous blood sample for procoagulant assays will be taken by a trained phlebotomist/ nurse using Vacutainer tubes from the subject approximately within 24 hours prior to the planned platelet transfusion (for both "control" and "treatment" arms). Post-transfusion venous blood sample for procoagulant assays will be taken by a trained phlebotomist or nurse using Vacutainer tubes form the subject at 1-4 hour after transfusion.

Incidence of all grades of bleeding (as defined on WHO bleeding scale)

Total number and type of blood products transfused

For each thrombocytopenic period, subject may receive platelets and other types of blood components. The time and type of blood components administered (including the non-study ones) would be recorded.

Full Information

NCT ID

NCT05067608

First Posted

August 2, 2021

Last Updated

September 23, 2021

Sponsor

Singapore General Hospital

Collaborators

DSO National Laboratories, Health Sciences Authority, Singapore

1. Study Identification

Unique Protocol Identification Number

NCT05067608

Brief Title

Study on the Safety and Efficacy of Cryopreserved Platelets in Hypoproliferative Thrombocytopenic Patients

Official Title

Study on the Safety and Efficacy of Cryopreserved Platelets in Hypoproliferative Thrombocytopenic Patients

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

October 25, 2019 (Actual)

Primary Completion Date

March 24, 2021 (Actual)

Study Completion Date

March 24, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Singapore General Hospital

Collaborators

DSO National Laboratories, Health Sciences Authority, Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to study the safety and efficacy of pooled buffy-coat derived platelets which had been frozen with dimethyl sulphoxide (DMSO), in the prevention of bleeding for patients with hypoproliferaitve thrombocytopenia. These platelets are hereafter referred to as cryopreserved platelets. Patients who have severely low platelet count due to impaired bone marrow function from chemotherapy or certain haematological conditions may need platelet transfusion to prevent spontaneous bleeding. Currently, platelets are stored in liquid form, and must be used within five to seven days of collection. In this study, DMSO is used to preserve platelets during freezing so that they can be stored for longer than five to seven days. Investigators hope to learn if thawed cryopreserved platelets are functional and safe for transfusion in humans.

Detailed Description

Platelets are currently stored in liquid form for a maximum of five to seven days. To extend the shelf-life of platelets, DMSO is added to freeze platelets for long-term storage. In vitro studies have shown that such cryopreserved platelets can be kept for at least two years at -80oC. This study is a clinical trial that aims to primarily assess the safety of cryopreserved pooled buffy coat-derived platelets in patients with hypoproliferative thrombocytopenia and no platelet refractoriness. Subjects will be randomised into two arms either a liquid platelet (control) or frozen platelet arm (treatment) and may receive four or more platelet transfusions per thrombocytopenic cycle. Each subject may participate in the study for up to two thrombocytopenic period, assuming a wash-out period of at least five days (during which the subject receives no platelet transfusions) between the two thrombocytopenic periods. If subjects participate in the study for more than one thrombocytopenic period, they will automatically be enrolled in the opposing arm for their second thrombocytopenic period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypoproliferative Thrombocytopenia

Keywords

Hypoproliferative thrombocytopenia, Cryopreserved, Transfusion, Platelets, Safety, Efficacy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Model Description

This is a phase 1b/2a single centre clinical trial. Eligible hypoproliferative thrombocytopenic adult patients enrolled in the study will be randomised into two arms. One arm is the "treatment" arm using cryopreserved platelets and the second is the "control" arm using liquid platelets. A recruitment period of two years is expected for 17 subjects in each arm. Subjects will automatically be crossed over to the other treatment arm once they have completed the first treatment arm and there is at least a 5-days interval without platelet transfusion. Subjects can be both inpatient and outpatient. During the thrombocytopenic period of 28 days, subjects may be required to have multiple platelet transfusions during this period.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control arm

Arm Type

Active Comparator

Arm Description

Arm Title

Treatment arm

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Control arm receiving normal (never before frozen) platelets as per current clinical practice

Intervention Description

Liquid platelets arm (control) and may receive multiple platelet transfusions per thrombocytopenic cycle.

Intervention Type

Biological

Intervention Name(s)

Treatment arm receiving cryopreserved platelets

Intervention Description

Cryopreserved platelets arm (treatment) and may receive multiple platelet transfusions per thrombocytopenic cycle.

Primary Outcome Measure Information:

Title

Incidence of adverse events related to platelet transfusion.

Description

Time Frame

Monitoring will be for 24 hours (serum test 18-30 hours) post-transfusion.

Title

Non-cutaneous Grade 2 or higher bleeding (as defined on the WHO bleeding scale)

Description

Time Frame

Each thrombocytopenic period is up to 28 days from the first prophylactic platelet transfusion (shorter if platelet count recovers above target level before 28 days)

Secondary Outcome Measure Information:

Title

Platelet count increase (absolute increase and corrected count increment) post-platelet trantrsfusion

Description

Time Frame

Within approximately 24 hours prior, 1-4 hour and 18-30 hour post-transfusion.

Title

Changes in platelet activity (measured by viscoelastic hemostatic assay) post-platelet transfusion

Description

Time Frame

Within approximately 24 hours prior, 1-4 hour and 18-30 hour post-transfusion.

Title

Changes in procoagulant activity post-platelet transfusion

Description

Time Frame

Within approximately 24 hours prior and 1-4 hour post-transfusion.

Title

Incidence of all grades of bleeding (as defined on WHO bleeding scale)

Description

Time Frame

Each thrombocytopenic period is up to 28 days from the first prophylactic platelet transfusion of each arm (shorter if platelet count recovers above target level before 28 days)

Title

Total number and type of blood products transfused

Description

Time Frame

Each thrombocytopenic period is up to 28 days from the first prophylactic platelet transfusion of each arm (shorter if platelet count recovers above target level before 28 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 21 years of age Be able to provide written informed consent Current or potential hypoproliferative thrombocytopenia with expected platelet count of <20 X 109/L for a minimum of 5 days in a 28-day period If pre-menopausal female of child bearing potential, then the subject must have a negative serum pregnancy test prior to study commencement, and must be using an acceptable method of contraception during the study. Calculated creatinine clearance of >30 ml/min (as calculated based on the Cockcroft-Gault equation; National Kidney Foundation 2017) at the point of recruitment, and within one week before transfusion Exclusion Criteria: Not meeting the inclusion criteria specified above Pregnant Breastfeeding Current platelet refractoriness History of allergy or adverse reaction to DMSO History of veno-occlusive disease History of acute venous or arterial thromboembolism within the last 3 months. History of unprovoked venous thromboembolism On antiplatelets, NSAIDs or anticoagulants within 1 week, and TCM (traditional Chinese medicine) which are known to decrease platelet count or platelet function or increase bleeding tendency within 2 weeks of study enrolment. Received or will be receiving L-asparaginase chemotherapy within 7 days of platelet transfusion Renal impairment with calculated creatinine clearance of <30ml/min. Non-cutaneous Grade 2 and above bleeding at the time of study assessment Presently with or a history of acute promyelocytic leukemia (APML), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), haemolytic-uremic syndrome (HUS), or any thrombotic microangiopathy (TMA) Presently with or a history of heparin-induced thrombocytopenia Presently with disseminated intravascular coagulation (DIC) or other risk factor(s) for bleeding other than thrombocytopenia (including platelet dysfunction, PT ≥ 1.3 X upper limit of normal for the laboratory, PTT ≥ 1.3 X upper limit of normal for the laboratory, or fibrinogen ≤ 1 g/L) History of anaphylaxis from blood transfusion Involved in any other therapeutic clinical trials in the last 6 months prior to the start of this research Concomitant participation in other therapeutic clinical trials during the full period of this study Receiving non-trial-related medication that might compromise transfusion safety Known history of congenital bleeding disorder Subject who declined to consent for platelet transfusion

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ang Ai Leen

Organizational Affiliation

Singapore General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Singapore General Hospital

City

Singapore

ZIP/Postal Code

169608

Country

Singapore

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Will not be sharing individual participant data collected in this study to other researchers.

Citations:

Citation

ClinicalTrials.gov: NCT02078284. Phase 1 safety study of dimethyl sulphoxide cryopreserved platelets.

Results Reference

background

PubMed Identifier

21214584

Citation

Dumont LJ, Dumont DF, Unger ZM, Siegel A, Szczepiorkowski ZM, Corson JS, Jones MK, Christoffel T, Pellham E, Bailey SL, Slichter SJ; BEST Collaborative. A randomized controlled trial comparing autologous radiolabeled in vivo platelet (PLT) recoveries and survivals of 7-day-stored PLT-rich plasma and buffy coat PLTs from the same subjects. Transfusion. 2011 Jun;51(6):1241-8. doi: 10.1111/j.1537-2995.2010.03007.x. Epub 2011 Jan 7.

Results Reference

background

PubMed Identifier

22882530

Citation

Dumont LJ, Cancelas JA, Graminske S, Friedman KD, Vassallo RR, Whitley PH, Rugg N, Dumont DF, Herschel L, Siegal AH, Szczepiorkowski ZM, Fender L, Razatos A. In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new platelet additive solution. Transfusion. 2013 May;53(5):972-80. doi: 10.1111/j.1537-2995.2012.03841.x. Epub 2012 Aug 6.

Results Reference

background

PubMed Identifier

27959967

Citation

Noorman F, van Dongen TT, Plat MJ, Badloe JF, Hess JR, Hoencamp R. Transfusion: -80 degrees C Frozen Blood Products Are Safe and Effective in Military Casualty Care. PLoS One. 2016 Dec 13;11(12):e0168401. doi: 10.1371/journal.pone.0168401. eCollection 2016.

Results Reference

background

PubMed Identifier

25439164

Citation

Slichter SJ, Jones M, Ransom J, Gettinger I, Jones MK, Christoffel T, Pellham E, Bailey SL, Corson J, Bolgiano D. Review of in vivo studies of dimethyl sulfoxide cryopreserved platelets. Transfus Med Rev. 2014 Oct;28(4):212-25. doi: 10.1016/j.tmrv.2014.09.001. Epub 2014 Sep 21.

Results Reference

background

Learn more about this trial

Study on the Safety and Efficacy of Cryopreserved Platelets in Hypoproliferative Thrombocytopenic Patients

We'll reach out to this number within 24 hrs