Transfusion Reduction in High-Bleeding-Risk Cardiac Surgery With Desmopressin

NCT07012837 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: IABF-10-05-25
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale Bleeding after cardiac surgery is a complication that might result in increased morbidity, mortality, and cost of cardiac surgery by 1.76 (confidence interval (CI), 1.64-1.90) times and a median increase in costs by Australian $33,338 (CI, $21,943-$38,415) \[1\]. Strategies and techniques to reduce postoperative bleeding in identified high-risk patients for bleeding after cardiac surgery might improve outcomes and resource utilization. Desmopressin (DDAVP) is used as a hemostatic agent to prevent and treat bleeding in patients with mild hemophilia patients with von Willebrand's deficiency through stimulating the release of von Willebrand factor from endothelial cells. Previous studies showed controversial results in terms of reduced transfusion requirements in patients with low risk for bleeding with post cardiopulmonary bypass (CPB) bleeding following prophylactic infusing desmopressin over 10 to 15 minutes after induction of anesthesia or protamine administration due to its positive effects on the coagulation system responsible for such bleeding. Contradictory, prophylactic desmopressin use demonstrated fewer transfusion requirements in patients treated with antiplatelets, which raises the need to examine its efficacy in high-risk cardiac surgery patients for perioperative bleeding. These controversial results might be attributed to delayed administration of desmopressin after evolving CPB-associated thrombocytopenia, platelet dysfunction, coagulation factor consumption and dilution, hyperfibrinolysis, and hypofibrinogenemia \[2\] Concerns were raised about the associated transient decreases in systemic vascular resistance and blood pressure after desmopressin administration following discontinuing CPB and administering protamine, which might be related to the rapid infusion rate during the critical surgery stage. The cost of a single dose of Desmopressin 0.3 ug/kg for a patient with an average weight of 70 Kg is about 82US$ which is cheaper than the alternative hemostatic agents proved to be effective in reducing bleeding and transfusion needs after cardiac surgery (e.g., fibrinogen concrete (average of 3 g = 1,167US$) and prothrombin complex concentrate (6,255US$ considering low fixed dosfixed-doseof 1040 IU F IX). It is yet unclear if extended infusions of desmopressin started earlier before the development of CPB-associated coagulopathy and platelets dysfunction from anesthesia induction time and continued to the end of CPB before protamine administration would offer an "efficacy," "safety, and "cost-effective" benefits over placebo in patients with high risks for bleeding after cardiac surgery terms of the need for transfusion, cumulative postoperative 48-hour chest tube outputs, need for reoperation, thrombotic complications, 30-day mortality, hemodynamic stability, and urine output during and after completing infusion, and costs of the study drug and allogenic transfusion requirement. That raises the need to examine its impact on these crucial clinical outcomes. Objective The primary objective of this prospective multicentre randomized clinical trial (RCT) is, compared with placebo, to examine the impact of prolonged infusion desmopressin on reducing postoperative bleeding and the need for allogenic allogeneic transfusion in high-bleeding-risk cardiac surgery patients scheduled for elective cardiac surgical procedures using CPB. Secondary objectives include comparing placebo and desmopressin in terms of safety and cost-effectiveness. Hypothesis It is hypothesized that extended 'desmopressin' infusion compared to 'placebo' results in less postoperative bleeding and transfusion needs (more effective) and leads to less hemodynamic compromise (safer) and cheaper (cost-effective) in high-risk cardiac surgery patients.

Conditions

Adult Patients Undergoing Cardiac Surgery; High Bleeding Risks; Planned Elective Cardiac Surgery Using CPB

Keywords

Adult cardiac surgery; Cardiopulmonary bypass; High bleeding risks; Desmopressin; Prophylactic; Point-of-care coagulation tests

Outcome Measures

Primary Outcomes (1)

• Cumulative 48-hour postoperative bleeding

  The primary outcome is the cumulative 48-hour postoperative bleeding, defined as the sum of estimated intraoperative salvaged blood and blood loss and postoperative chest tube output for 48 hours from surgery. Intraoperative blood loss was calculated from the total volume in suction bottles (minus the volume of irrigating solution), weighed sponges, and the volume collected in the Cell-Saver reservoir (minus the volume of anticoagulant solution). After the chest is closed, hourly postoperative blood loss will be calculated from the chest tubes and drain reservoirs.

  Intraoperative and for 48 hours after surgery

Secondary Outcomes (28)

• The need for allogenic PRBCs transfusion

  For 7 days after surgery

• The need for allogenic transfusion of fresh frozen plasma

  For the first 7 days after surgery

• The need for allogenic individual and pooled platelet units

  For the first 7 days after surgery

• The need for allogenic cryoprecipitates units

  For the first 7 days after surgery

• The need for Recombinant Factor VIII administration

  For the first 7 days after surgery

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Before induction of anesthesia, patients will receive identical and similar clear study solutions in similar size transparent 50-cc bags, including Saline will be infused over five hours at a rate of 10 ml/hr. The local pharmacists who will not be involved in patients' care or data collection will prepare the study solution.

Drug: Placebo

Desmopressin

ACTIVE COMPARATOR

Before induction of anesthesia, patients will receive identical and similar clear study solutions in similar size transparent 50-cc bags, including Desmopressin 0.3 ug/kg of the patient's body weight will be infused over five hours at a rate of 10 ml/hr. The local pharmacists who will not be involved in patients' care or data collection will prepare the study solution.

Drug: Desmopresin

Interventions

Placebo DRUG

Before induction of anesthesia, patients will receive identical and similar clear study solutions in similar size transparent 50-cc bags, including Saline will be infused over five hours at a rate of 10 ml/hr. The local pharmacists who will not be involved in patients' care or data collection will prepare the study solution.

Placebo

Desmopresin DRUG

Before induction of anesthesia, patients will receive identical and similar clear study solutions in similar size transparent 50-cc bags, including Desmopressin 0.3 ug/kg of the patient's body weight will be infused over five hours at a rate of 10 ml/hr. The local pharmacists who will not be involved in patients' care or data collection will prepare the study solution.

Desmopressin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult 18 years or older.
• Scheduled for any type of elective cardiac surgery.
• Using CPB.
• General anesthesia is provided in an endotracheally intubated patient.
• A high risk of postoperative bleeding is defined as any of the following \[21-23\];
• Redo or repeated surgery.
• Treatment with platelet P2Y12 receptor--inhibiting drugs was discontinued for 7 days (ticlopidine, clopidogrel, and prasugrel) or 5 days (ticagrelor).
• Any known coagulation disorders.
• Hypofibrinogenemia less than 150 mg/dl.
• Platelet count \<100.000 cells/μL.
• Chronic renal failure, whether dialysis-dependent or not.
• Liver cell failure Child-Pugh class B or C or the Model for End-Stage Liver Disease (MELD) \>=29
• Infective endocarditis.
• Acute type-A aortic dissection.
• Expected surgery with CPB time longer than 150 minutes.

You may not qualify if:

• Planned for cardiac surgery without CPB;
• Planned for a combined coronary revascularization surgery and a valve or intra-cardiac surgery;
• Pregnancy;
• Consent for another interventional study during anesthesia;
• No written informed consent;
• Preoperative need for mechanical circulatory support;

Sponsors & Collaborators

• Imam Abdulrahman Bin Faisal University: lead
• Johns Hopkins Aramco Healthcare: collaborator

Study Sites (1)

Imam Abdulrahamn Bin Faisal University (Former, Dammam University)

Dammam, Eastern Province, 31952, Saudi Arabia

Location

Related Publications (25)

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  BACKGROUND

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Study Officials

• Mohamed R El Tahan, MD

  Imam Abdulrahman Bin Faisal University

  STUDY CHAIR

• Fahad Makhdoum, MD

  Imam Abdulrahman Bin Faisal University

  PRINCIPAL INVESTIGATOR

• Yasser F ElGhoneimy, MD

  Imam Abdulrahman Bin Faisal University

  STUDY DIRECTOR

Central Study Contacts

Mohamed R El Tahan, MD

CONTACT

0096569371849; mohamedrefaateltahan@yahoo.com

Yasser F ElGhoneimy, MD

CONTACT

+966 59 777 7012; yfarag@iau.edu.sa

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Further minimization of bias will be achieved by involving two independent investigators. The researcher who is not responsible for providing anesthesia or performing surgery will perform the Randomization directly before the start of anesthesia. A second investigator, blinded for the randomization arm, will record the primary and secondary postoperative outcome measures.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Cardiac Anesthesia

Model Details: A multicenter, parallel, two-group, prospective, multicenter, randomized, blinded comparative trial in patients with high risks of postoperative bleeding scheduled for elective cardiac surgery at the King Fahad Hospital of Imam Abdulrahman Bin Faisal University, Al Khobar and Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.

Study Record Dates

• First Submitted: June 1, 2025
• First Posted: June 10, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Beginning six months after publication and for a period of five years.
• Access Criteria: Data access will be granted following review and approval of a research proposal and the signing of a data access agreement. Requests should be directed to the corresponding author.

Locations

SA (1)