Cold-Stored vs Room Temperature Platelets for Cardiac Surgery

(PLTS-1 Trial)

Recruiting at 1 trial location

Overseen By Deep Grewal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Warfarin, Antiplatelets, Direct oral anticoagulants

Disqualifiers: Hemostatic disorders, Pregnancy, Hemodynamic instability, 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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if cold-stored platelets, specifically Delayed Cold-Stored Buffy Coat Platelets, perform as well as room temperature platelets for patients undergoing heart surgery. Researchers seek to identify which type of platelet better reduces the need for additional blood products within a day after surgery. This information could be crucial for patients requiring platelet transfusions, such as those undergoing complex surgeries or with low preoperative platelet counts. Eligible participants include adults scheduled for specific types of elective heart surgeries. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before surgery. You must not be on warfarin or direct oral anticoagulants within 3 days prior to surgery, and you must not take antiplatelet drugs (except aspirin) within 5 days prior to surgery.

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

Research shows that storing platelets in the cold might be safer in some ways than keeping them at room temperature. One study found that cold-stored platelets could lower the risk of bacterial contamination, which can cause infections during transfusions, because cooler temperatures make it harder for bacteria to grow.

However, concerns remain. In a study with 713 adults who had heart surgery, those who received cold-stored platelets needed more blood transfusions after surgery compared to those who received room-temperature platelets. This suggests differences in how well the two types stop bleeding.

Overall, cold-stored platelets might help reduce infection risk, but questions remain about their effectiveness during surgery. Current trials are examining these safety and effectiveness issues further. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for cardiac surgery-related platelet needs involve using room temperature platelets, which are maintained at 22°C for up to 7 days. However, researchers are excited about the potential of using delayed cold-stored platelets. This innovative approach involves initially storing platelets at room temperature and then switching to cold storage (4°C) for at least 24 hours, extending their usability up to 14 days. This method could potentially improve platelet availability and reduce waste, offering a more efficient and longer-lasting option compared to current standards.

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

This trial will compare Delayed Cold-Stored Buffy Coat Platelets with Room Temperature Buffy Coat Platelets for cardiac surgery patients. Studies have shown that cold storage might enhance platelet clotting function compared to room temperature storage. Research suggests that cold-stored platelets may last longer and remain effective at stopping bleeding. In lab tests, cold-stored platelets retained their clotting ability better than those stored at room temperature. However, a study with 713 heart surgery patients linked cold-stored platelets to a higher need for blood transfusions after surgery compared to room-temperature ones. These mixed results indicate that while cold storage has potential benefits, further research is needed to fully understand its effectiveness in different situations. ^{1 2 3 4 5}

Who Is on the Research Team?

Justyna Bartoszko, MD

Principal Investigator

University Health Network, Toronto

Jeannie Callum, MD

Principal Investigator

Queen's University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need elective cardiac surgery with CPB (heart-lung machine support). It's specifically for those at high risk of bleeding, like patients with low platelet counts or undergoing complex surgeries such as multiple valve repairs or aorta replacement.

Inclusion Criteria

I am scheduled for complex surgery or have a low platelet count.

I have had a complex heart surgery involving valves or aorta.

I am 18 or older and scheduled for heart surgery with a heart-lung machine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either cold-stored or room temperature-stored platelets during cardiac surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Delayed Cold-Stored Buffy Coat Platelets
• Room Temperature Buffy Coat Platelets

Trial Overview The PLTS-1 study compares two types of platelet storage methods: cold-stored and room temperature. The goal is to see if cold-stored platelets are just as good at preventing bleeding after heart surgery using CPB as the standard room temp stored ones.

How Is the Trial Designed?

Group I: Intervention Group Experimental Treatment 1 Intervention

Patients randomized to the Delayed Cold-Stored Platelet Group will receive ABO-identical buffy-coat platelets (pathogen reduced products) maintained at 22°C for up to 4 days then placed at 4°C for a minimum of 1 day (24 hours), with expiration at 14 days after collection.

Group II: Control Group Active Control 1 Intervention

Those randomized to the Room Temperature Platelet Group will receive ABO-identical buffy-coat platelets (pathogen reduced products) maintained at 22°C for up to 7 days (as per current standard of care).

Delayed Cold-Stored Buffy Coat Platelets is already approved in United States, Canada for the following indications:

Approved in United States as Cold-Stored Platelets for:

• Trauma patients with hemorrhagic shock
• Cardiac surgical patients with acute bleeding

Approved in Canada as Cold-Stored Platelets for:

• Cardiac surgical patients with acute bleeding

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Canadian Blood Services

Collaborator

Trials

24

Recruited

39,200+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Published Research Related to This Trial

Buffy coats (BCs) stored in containers with low gas permeability showed significant accumulation of CO2 and a rapid decrease in pH, which can negatively affect the quality of platelet concentrates (PCs).

Continuous mixing during storage led to increased red cell damage without clear benefits, suggesting that BCs should ideally be stored for 24 hours or less to maintain platelet viability and minimize activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Storage of buffy coat preparations at 22 degrees C in plastic containers with different gas permeability. Eriksson, L., Eriksson, G., Högman, CF.[2019]

In a study of 713 adults undergoing cardiac surgery, delayed cold-stored platelets were linked to higher rates of postoperative transfusions compared to room temperature-stored platelets, with 44% of patients receiving delayed cold-stored platelets requiring additional transfusions within the first 24 hours.

Despite the increased transfusion rates, there were no significant differences in clinical outcomes such as reoperation for bleeding or chest tube output, suggesting that while delayed cold-stored platelets can be used in critical situations, they may not be the best first choice for transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Transfusions after Administration of Delayed Cold-stored Platelets versus Room Temperature Platelets in Cardiac Surgery: A Retrospective Cohort Study. Klompas, AM., Zec, S., Hanson, AC., et al.[2023]

Cold-stored platelets and delayed-cold platelets (stored at room temperature for 4 days before refrigeration) maintained similar platelet counts and activation profiles over a 21-day period, indicating that delayed-cold storage could be a practical alternative.

Transferring platelets to refrigerated storage near their expiry date may help maximize platelet inventories without compromising their quality, making it a potential strategy for managing platelet supplies effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximising platelet availability by delaying cold storage. Wood, B., Johnson, L., Hyland, RA., et al.[2019]

Platelet concentrates prepared from buffy coats stored at 4 degrees C showed significantly lower recovery and survival rates in vivo compared to those from platelet-rich plasma stored at 22 degrees C, with recovery rates of 30.5% vs. 41.4% and survival times of 2.4 days vs. 7.0 days, respectively.

The study involved 8 healthy volunteers and highlights the importance of storage temperature for optimizing the efficacy of platelet concentrates, suggesting that storage at 22 degrees C is preferable for better platelet survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival in vivo of platelets stored for 48 hours in the buffycoat at 4 degrees C compared to platelet rich plasma stored at 22 degrees C. Pietersz, RN., Loos, JA., Reesink, HW.[2019]

Cold-stored platelets (CSP) have been shown to maintain better hemostatic function and adhesion properties compared to standard room-temperature platelets (RTP), making them potentially more effective for patients undergoing cardiac surgery.

CSP also offer advantages such as a longer shelf-life and a lower risk of bacterial contamination, but further large clinical trials are necessary to confirm their benefits in treating acute bleeding situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review. Lu, J., Karkouti, K., Peer, M., et al.[2023]

Platelet concentrates (PCs) made from overnight-stored buffy coats showed similar platelet yield to those made from fresh blood, suggesting they could be effectively used in clinical settings.

Stored PCs from overnight-stored buffy coats demonstrated better aggregation at lower temperatures (25 degrees C) compared to higher temperatures (37 degrees C), indicating potential advantages in storage conditions for maintaining platelet function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Storage of platelet concentrates from overnight-stored blood and overnight-stored buffy coat: in vitro studies. Rácz, Z., Baróti, C.[2019]

Storing buffy coats overnight at room temperature results in a higher platelet yield and white blood cell count compared to fresh buffy coats held for only 2 hours, indicating a potential advantage for platelet concentrate production.

However, the overnight storage also leads to increased levels of lactate and LDH, suggesting that while the yield is higher, there may be some storage-related changes that could affect the quality of the platelets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of platelet concentrates prepared after two hours and overnight storage of buffy coat at room temperature. Ojha, S., Tirlotkar, A., Gupta, AM., et al.[2021]

Cold-stored platelets can be stored for up to 20 days, showing better preservation of certain platelet functions compared to standard room temperature-stored platelets, particularly in terms of integrin activation and mitochondrial integrity.

However, platelet recovery declines significantly after 10 days of cold storage, indicating that while cold storage may extend shelf life, its effectiveness in clinical applications still needs to be validated in bleeding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C-stored platelets. Stolla, M., Bailey, SL., Fang, L., et al.[2020]

Cold-stored platelets (CS-PLTs) were approved for use in actively bleeding trauma patients, with initial FDA approval for a 3-day storage period without agitation, highlighting their potential for improved hemostatic outcomes compared to room temperature platelets.

Despite the approval, a high discard rate of 80.9% was observed due to clot formation during storage, indicating a need for advancements like pathogen-reduced solutions to extend shelf life and reduce contamination risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold platelets for trauma-associated bleeding: regulatory approval, accreditation approval, and practice implementation-just the "tip of the iceberg". Stubbs, JR., Tran, SA., Emery, RL., et al.[2018]

Platelet concentrates (PCs) prepared from buffy coats (BCs) held at room temperature for up to 12 hours maintain their quality for up to 5 days in plasma, showing no detrimental effects on key quality indicators like pH and morphology.

Extending the holding time from 3 to 12 hours improved the preservation of platelet activation markers and enhanced thrombin-induced aggregation, suggesting that longer holding times can be beneficial for platelet function without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of a 12-hour, 22 degrees C holding period for buffy coats on the preparation of platelet concentrates stored in plasma. Boeri, N., Saleun, S., Pelissier, E., et al.[2019]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/17/2023/546600/Chilling-controversy-cold-stored-platelets-for

cold-stored platelets for prophylactic transfusions | Blood Many in vitro studies suggest that cold storage preserves the platelet hemostatic function better than room temperature storage, which could improve transfused ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11179374/

Delayed cold-stored vs. room temperature stored platelet ... Cold storage (at 1–6 °C) of platelets prolongs their shelf-life while maintaining hemostatic effectiveness in acutely bleeding patients. Thus, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06147531

NCT06147531 | Delayed Cold-Stored Platelets -PLTS-1 PLTS-1 is a multicentre, randomized, controlled, pilot trial, using a conventional, parallel group, two-armed design at 2 cardiac surgery centres in Canada.

4. withpower.com withpower.com/trial/phase-2-cardiopulmonarybypass-11-2023-0b476

Cold-Stored vs Room Temperature Platelets for Cardiac ... In a study of 713 adults undergoing cardiac surgery, delayed cold-stored platelets were linked to higher rates of postoperative transfusions compared to room ...

5. researchgate.net researchgate.net/publication/381460067_Delayed_cold-stored_vs_room_temperature_stored_platelet_transfusions_in_bleeding_adult_cardiac_surgery_patients-a_randomized_multicentre_pilot_study_PLTS-1

Delayed cold-stored vs. room temperature stored platelet ... The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass ...