Clinical trial NCT05067608: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hypoproliferative Thrombocytopenia
Keywords: Hypoproliferative thrombocytopenia
Cryopreserved
Transfusion
Platelets
Safety
Efficacy
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
Collaborators: name: DSO National Laboratories
name: Health Sciences Authority, Singapore
First posted: 2021-10-05
Enrollment: 17
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. ≥ 21 years of age
2. Be able to provide written informed consent
3. 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
4. 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.
5. 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:

1. Not meeting the inclusion criteria specified above
2. Pregnant
3. Breastfeeding
4. Current platelet refractoriness
5. History of allergy or adverse reaction to DMSO
6. History of veno-occlusive disease
7. History of acute venous or arterial thromboembolism within the last 3 months.
8. History of unprovoked venous thromboembolism
9. 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.
10. Received or will be receiving L-asparaginase chemotherapy within 7 days of platelet transfusion
11. Renal impairment with calculated creatinine clearance of \<30ml/min.
12. Non-cutaneous Grade 2 and above bleeding at the time of study assessment
13. 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)
14. Presently with or a history of heparin-induced thrombocytopenia
15. 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)
16. History of anaphylaxis from blood transfusion
17. Involved in any other therapeutic clinical trials in the last 6 months prior to the start of this research
18. Concomitant participation in other therapeutic clinical trials during the full period of this study
19. Receiving non-trial-related medication that might compromise transfusion safety
20. Known history of congenital bleeding disorder
21. Subject who declined to consent for platelet transfusion

Primary outcomes:
measure: Incidence of adverse events related to platelet transfusion.
timeFrame: Monitoring will be for 24 hours (serum test 18-30 hours) post-transfusion.
measure: Non-cutaneous Grade 2 or higher bleeding (as defined on the WHO bleeding scale)
timeFrame: 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 outcomes:
measure: Platelet count increase (absolute increase and corrected count increment) post-platelet trantrsfusion
timeFrame: Within approximately 24 hours prior, 1-4 hour and 18-30 hour post-transfusion.
measure: Changes in platelet activity (measured by viscoelastic hemostatic assay) post-platelet transfusion
timeFrame: Within approximately 24 hours prior, 1-4 hour and 18-30 hour post-transfusion.
measure: Changes in procoagulant activity post-platelet transfusion
timeFrame: Within approximately 24 hours prior and 1-4 hour post-transfusion.
measure: Incidence of all grades of bleeding (as defined on WHO bleeding scale)
timeFrame: 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)
measure: Total number and type of blood products transfused
timeFrame: 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)
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Singapore General Hospital
name: Ang Ai Leen
role: PRINCIPAL_INVESTIGATOR
References:
citation: ClinicalTrials.gov: NCT02078284. Phase 1 safety study of dimethyl sulphoxide cryopreserved platelets.
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.
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.
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.
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.