Cryopreserved Platelets for Cardiac Surgery

(CRYPTICS Trial)

No longer recruiting at 18 trial locations

Overseen By Anna Yu

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Cellphire, Inc.

Disqualifiers: CABG alone, VAD, Aneurysm, Thrombosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day (Day of Surgery)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether cryopreserved platelets (platelets stored by freezing) perform as well as or better than the usual liquid-stored platelets in reducing blood loss during heart surgeries that require a heart-lung machine. The study includes two groups: one receiving cryopreserved platelets and the other receiving liquid-stored platelets. It seeks participants undergoing heart surgery with a high risk of bleeding, such as repeat heart operations or complex surgeries. As a Phase 2/3 trial, this study measures the treatment's effectiveness and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in heart surgery care.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators or your doctor for guidance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown limited information on the safety of frozen platelets compared to regular ones stored in liquid for surgery-related bleeding. Earlier studies primarily focused on the effectiveness of frozen platelets in stopping bleeding, rather than their safety. However, their inclusion in the current phase of trials indicates some safety demonstrated in earlier research. This suggests they might be safe enough for further testing in surgical patients. It's important to note that frozen platelets aren't widely used yet, as more research is needed to confirm their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cryopreserved platelets for cardiac surgery because they offer a unique preservation method that extends shelf life compared to traditional liquid-stored platelets. This means they can be stored longer, potentially improving availability during surgeries. Additionally, cryopreservation may enhance platelet function post-thaw, possibly leading to better patient outcomes after cardiac procedures. Unlike liquid-stored options, cryopreserved platelets could provide more flexibility and effectiveness in critical surgical settings.

What evidence suggests that this trial's treatments could be effective for controlling blood loss in cardiac surgery?

This trial will compare cryopreserved platelets with liquid-stored platelets for cardiac surgery. Research has shown that frozen platelets can help reduce blood loss during heart surgery. In one study, patients who received frozen platelets lost less blood than those who received regular stored platelets, even though their platelet count didn't increase as much after the transfusion. However, another study found that frozen platelets were about 30% less effective at helping blood clot normally. Despite this, survival rates 30 days after surgery were similar for both groups. Overall, frozen platelets appear to be a promising option for managing blood loss during surgery. ^{1 3 5 6 7}

Who Is on the Research Team?

Allan Alexander, MD

Principal Investigator

Cellphire Therapeutics, Inc.

Kenichi Tanaka, MD

Principal Investigator

University of Oklahoma

Robert Kramer, MD

Principal Investigator

MaineHealth

Are You a Good Fit for This Trial?

Adults at least 18 years old undergoing cardiopulmonary bypass surgery with a risk of post-surgical bleeding can join. They must understand and agree to the study's terms, use effective birth control if applicable, and be likely to need platelets during surgery. Those with coronary artery bypass alone, ventricular assist device implantation, certain health conditions or allergies cannot participate.

Inclusion Criteria

I have had more than one heart surgery.

My surgery is likely to require a platelet transfusion.

I have had heart surgery involving valves or bypass.

Exclusion Criteria

I am scheduled for or have had a specific surgery.

I have had coronary artery bypass surgery.

History of heparin-inducted thrombocytopenia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Cryopreserved Platelets or Liquid Stored Platelets intraoperatively or post-operatively during Cardiopulmonary Bypass Surgery

1 day (Day of Surgery)

1 visit (in-person)

Efficacy Follow-up

Monitoring of chest tube drainage and other efficacy endpoints post-surgery

24 hours post time zero

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Human platelets

Trial Overview The trial is testing whether Cryopreserved Platelets are as good as or better than Liquid Stored Platelets for controlling blood loss in patients having heart surgery involving cardiopulmonary bypass. Participants will randomly receive one of the two platelet types.

How Is the Trial Designed?

Group I: Cryopreserved platelets Experimental Treatment 1 Intervention

Cryopreserved platelets to be given intraoperatively or post operatively up to 3 units post-heparin reversal

Group II: Liquid stored platelets Active Control 1 Intervention

Liquid stored platelets to be given intraoperatively or post operatively up to 3 units post-heparin reversal

Human platelets is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Human Platelets for:

• Bleeding disorders
• Cardiopulmonary bypass surgery
• Thrombocytopenia

Approved in European Union as Human Platelets for:

• Bleeding disorders
• Cardiopulmonary bypass surgery
• Thrombocytopenia
• Haematopoietic stem cell transplantation

Approved in Canada as Human Platelets for:

• Bleeding disorders
• Cardiopulmonary bypass surgery
• Thrombocytopenia

Approved in Japan as Human Platelets for:

• Bleeding disorders
• Cardiopulmonary bypass surgery
• Thrombocytopenia

Who Is Running the Clinical Trial?

Cellphire, Inc.

Lead Sponsor

Trials

5

Recruited

260+

Cellphire Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

300+

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

Published Research Related to This Trial

Cryopreserved platelets, stored at -80 °C for up to two years using dimethylsulfoxide as a cryoprotectant, can serve as a valuable emergency backup for platelet supply, especially in challenging logistics like rural or military areas.

Despite their procoagulant properties and faster thrombin and fibrin formation, cryopreserved platelets show low post-transfusion recovery rates, indicating rapid clearance from circulation, which may be linked to changes in the GPIbα receptor. Further research is needed to understand the clinical implications of these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet Biochemistry and Morphology after Cryopreservation. Six, KR., Compernolle, V., Feys, HB.[2020]

Cryopreserved platelets (CPPs) stored at -80 °C enhance the exposure of phosphatidylserine (PS) on their surface, which promotes phagocytosis by macrophages and triggers an inflammatory response, potentially leading to adverse reactions during transfusion.

CPPs were found to activate THP-1 cells more effectively than platelets stored at higher temperatures, resulting in increased secretion of proinflammatory cytokines like TNF-α and IL-1β, indicating a need for careful monitoring of CPP transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreserved platelets augment the inflammatory response: role of phosphatidylserine- and P-selectin-mediated platelet phagocytosis in macrophages. Zhao, J., Xu, B., Chen, G., et al.[2020]

Cryopreserved platelets (cryoplatelets) from different manufacturing sites showed significantly reduced adhesion compared to noncryopreserved controls, indicating potential limitations in their function during blood clotting.

The study found that cryopreservation leads to a specific subset of platelets with altered receptor expression and reduced integrin activation, which may affect their effectiveness in hemostasis, although the clinical implications of these changes need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between manufacturing sites shows differential adhesion, activation, and GPIbα expression of cryopreserved platelets. Six, KR., Delabie, W., Devreese, KMJ., et al.[2019]

This ongoing multicenter, randomized, blinded trial aims to compare the effectiveness of cryopreserved platelets versus liquid stored platelets in reducing blood loss during cardiac surgery with cardiopulmonary bypass, focusing on patients at risk for significant bleeding.

If proven effective and safe, cryopreserved platelets could significantly extend the shelf life of stored platelets, improving availability in both military and civilian medical settings where liquid stored platelets may not be accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of the Randomized Controlled Trial Comparing Dimethyl Sulfoxide Cryopreserved Platelets to Liquid Stored Platelets in Patients Undergoing Cardiopulmonary Bypass Surgery. Whitman, G., Kramer, R., Tanaka, K., et al.[2023]

Cryopreservation of platelets using 6% dimethyl sulfoxide (DMSO) and storage at -80 °C can extend their shelf life from 7 days to 2 years, which is a significant improvement for clinical use.

Post-thaw analysis showed that platelets diluted with autologous plasma had a higher recovery rate and thrombin generation potential compared to those diluted with 0.9% NaCl, indicating better hemostatic function after cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey. Yılmaz, S., Çetinkaya, RA., Eker, İ., et al.[2019]

The study involving 33 research dogs found that cryopreserved platelets using Thrombosol did not improve in vivo survival or function compared to those preserved in 6% DMSO, indicating no added benefit from Thrombosol.

Both types of cryopreserved platelets showed significantly lower recovery and half-life compared to fresh platelets, suggesting that while cryopreservation allows for storage, it does not match the effectiveness of fresh platelets in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreservation of canine platelets. Appleman, EH., Sachais, BS., Patel, R., et al.[2016]

Platelet concentrates, while accounting for 10% of blood components, are linked to over 25% of adverse events, highlighting the need for improved safety measures during collection and storage.

Research indicates that whole blood buffy coat pooled platelets are safer than apheresis platelets, showing lower risks of infections and inflammatory reactions, suggesting a need to reconsider current transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving platelet transfusion safety: biomedical and technical considerations. Garraud, O., Cognasse, F., Tissot, JD., et al.[2018]

Platelets cryopreserved with ThromboSol and only 2% DMSO showed significantly better recovery (40.2%) and longer survival time (166.3 hours) compared to those preserved with the standard 6% DMSO method (28.8% recovery and 152.1 hours survival).

The use of ThromboSol not only enhances the effectiveness of platelet storage but also reduces the DMSO concentration needed, which could simplify the cryopreservation process and improve outcomes for thrombocytopenic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced circulatory parameters of human platelets cryopreserved with second-messenger effectors: an in vivo study of 16 volunteer platelet donors. Currie, LM., Lichtiger, B., Livesey, SA., et al.[2019]

A new method using CD34+ hematopoietic stem/progenitor cells from umbilical cord blood can generate megakaryocytes that produce functional platelets (PLTs) after being cryopreserved, showing promise for treating thrombocytopenia.

Infusing these megakaryocytic cells into immune-deficient mice resulted in the production of human PLTs that lasted significantly longer than traditional PLT transfusions, indicating a potential new source for platelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice. Patel, A., Clementelli, CM., Jarocha, D., et al.[2020]

In a study involving 17 patients undergoing operations with extracorporeal circulation, using cryopreserved autologous thrombocytes effectively prevented thrombohemorrhagic complications, demonstrating a clear hemostatic effect.

The method of plasma thrombocytapheresis not only prepared the autologous thromboconcentrate but also produced large amounts of autoplasma, which helped in managing blood loss during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of cryopreserved autologous thrombocytes in cardiac surgery]. Lytkin, MI., Shevchenko, IuL., Matveev, SA.[2016]

Cryopreservation of platelets allows for the storage and availability of functional platelets for transfusions, making it a practical option for hospitals with standard blood-banking facilities.

The study reports on 16 successful transfusions of frozen-thawed platelets, demonstrating the feasibility and effectiveness of this method in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet cryopreservation: a simple routine. Hocking, DR., Olsen, RE.[2004]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772641/

Cryopreserved platelets compared with liquid-stored platelets ... Blood loss in the patients who received cryopreserved platelets was significantly less, despite lower post-transfusion platelet increments and a ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666273622003795

Design of the Randomized Controlled Trial Comparing ... This design article describes an ongoing multicenter, randomized, blinded trial to evaluate noninferiority or superiority of cryopreserved platelets with liquid ...

3. aabb.org aabb.org/news-resources/news/article/2024/10/20/aabb24--clip-ii-trial-examines-cryopreserved-platelets

AABB24: CLIP-II Trial Examines Cryopreserved Platelets In closing, Reade observed that even though cryopreserved platelets proved to be 30% less effective in restoring hemostatic balance, their use ...

4. aob.amegroups.org aob.amegroups.org/article/view/6765/html

Cryopreserved platelets: a narrative review of its current role ... The 30-day survival rate in both groups of patients was similar (76% in the group receiving CPP and 81% in the group receiving liquid stored platelets). There ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03991481

NCT03991481 | The Cryopreserved vs. Liquid Platelets Trial The aim of the study is to assess the efficacy, safety and cost effectiveness of cryopreserved platelets, compared to conventional liquid-stored platelets, for ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36600425/

Cryopreserved platelets compared with liquid-stored ... Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding.

7. jtcvsopen.org jtcvsopen.org/article/S2666-2736(22)00379-5/fulltext

Design of the Randomized Controlled Trial Comparing ... This design article describes an ongoing multicenter, randomized, blinded trial to evaluate noninferiority or superiority of cryopreserved platelets with ...