Cryopreserved Platelets for Cardiac Surgery

(CRYPTICS Trial)

Recruiting at 17 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)

200 Participants Needed

Trial Summary

What is the purpose of this trial?

A randomized, parallel group, active comparator-controlled trial to evaluate the non-inferiority or superiority of Cryopreserved Platelets with Liquid Stored Platelets in controlling blood loss in patients undergoing Cardiopulmonary Bypass Surgery.

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.

What data supports the idea that Cryopreserved Platelets for Cardiac Surgery is an effective treatment?

The available research shows that cryopreserved platelets, especially those treated with ThromboSol, have better recovery and survival rates compared to those preserved with a higher concentration of DMSO. Specifically, ThromboSol-treated platelets had a 40.2% recovery rate and survived for 166.3 hours, compared to a 28.8% recovery rate and 152.1 hours survival for the standard method. Additionally, in cardiac surgery, cryopreserved platelets were effective in preventing bleeding complications, maintaining important blood characteristics. This suggests that cryopreserved platelets are a promising treatment option for cardiac surgery. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment 'Cryopreserved Platelets for Cardiac Surgery'?

Research shows that cryopreserved platelets, when treated with ThromboSol, have better recovery and survival rates compared to standard methods, suggesting they may be effective in maintaining blood clotting during cardiac surgery. ^{1 2 3 4 5}

What safety data is available for cryopreserved platelets used in cardiac surgery?

The safety data for cryopreserved platelets (CPPs) includes several studies. One study highlights that CPPs can extend shelf life to at least 2 years, but may augment inflammatory responses due to mechanisms like platelet phagocytosis by macrophages. Another review indicates that platelet transfusions can lead to adverse events, often due to platelet activation during collection and storage, but suggests that whole blood buffy coat pooled platelet components are safer than apheresis components. Additionally, a study on ThromboSolTM, a platelet-stabilizing formulation, shows improved recovery and survival times for cryopreserved platelets, suggesting enhanced safety and efficacy compared to traditional methods. Overall, while CPPs offer logistical advantages, their safety profile requires careful consideration of potential inflammatory and immunological reactions. ^{3 4 6 7 8}

Is it safe to use cryopreserved platelets in humans?

Cryopreserved platelets can cause an inflammatory response in the body, which is a reaction that can lead to swelling and redness. However, studies have shown that using certain methods to preserve platelets can improve their safety and effectiveness when transfused into humans. ^{3 4 6 7 8}

Is the treatment Human platelets promising for cardiac surgery?

Yes, cryopreserved human platelets are promising for cardiac surgery because they can be stored for a long time and used immediately when needed. They help prevent bleeding complications during surgery and maintain important blood functions. ^{2 4 9 10 11}

How is the treatment of cryopreserved platelets unique for cardiac surgery?

Cryopreserved platelets are unique because they can be stored for a long time and are immediately available when needed, unlike standard liquid-preserved platelets. This makes them particularly useful in cardiac surgery where there is a risk of significant bleeding, as they maintain their function after being frozen and thawed. ^{2 4 9 10 11}

Research Team

Allan Alexander, MD

Principal Investigator

Cellphire Therapeutics, Inc.

Kenichi Tanaka, MD

Principal Investigator

University of Oklahoma

Robert Kramer, MD

Principal Investigator

MaineHealth

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Platelet Biochemistry and Morphology after Cryopreservation. [2020]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Use of cryopreserved autologous thrombocytes in cardiac surgery]. [2016]

3. England 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. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Cryopreservation of canine platelets. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Pre-clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice. [2020]

6. Turkey pubmed.ncbi.nlm.nih.gov

Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Cryopreserved platelets augment the inflammatory response: role of phosphatidylserine- and P-selectin-mediated platelet phagocytosis in macrophages. [2020]

8. Italy pubmed.ncbi.nlm.nih.gov

Improving platelet transfusion safety: biomedical and technical considerations. [2018]

9. Australia pubmed.ncbi.nlm.nih.gov

Platelet cryopreservation: a simple routine. [2004]

10. United States pubmed.ncbi.nlm.nih.gov

Comparison between manufacturing sites shows differential adhesion, activation, and GPIbα expression of cryopreserved platelets. [2019]

11. Netherlands 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. [2023]