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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.

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

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

PlaceboDrug

Placebo

DesmopresinDrug

Study Sites (1)

Imam Abdulrahamn Bin Faisal University (Former, Dammam University)

Dammam, Eastern Province, 31952, Saudi Arabia

Mohamed R El Tahan, MDCONTACT00966569371849 mohamedrefaateltahan@yahoo.com

Fahad Makhdoum, MDCONTACTfmakhdom@gmail.com

Talal Alghamdi, MDSUB INVESTIGATOR

Maha Albrahim, M.SecSUB INVESTIGATOR

Fatimah Alqaysum, M.SecSUB INVESTIGATOR

Mohab M Manna, M.SecSUB INVESTIGATOR

Abdullah Halawani, MDSUB INVESTIGATOR

Abdulmohsen Alharbi, MDSUB INVESTIGATOR

Khaled AlGarni, MD

Related Publications (25)

Redfern RE, Fleming K, March RL, Bobulski N, Kuehne M, Chen JT, Moront M. Thrombelastography-Directed Transfusion in Cardiac Surgery: Impact on Postoperative Outcomes. Ann Thorac Surg. 2019 May;107(5):1313-1318. doi: 10.1016/j.athoracsur.2019.01.018. Epub 2019 Feb 12.

PMID: 30768933BACKGROUND

Khalil MA, El Tahan MR, Khidr AM, Fallatah S, Abohamar AD, Amer MM, Makhdom F, El Ghoneimy Y, Al Bassam B, Alghamdi T, Abdulfattah D. Effects of norepinephrine infusion during cardiopulmonary bypass on perioperative changes in lactic acid level (Norcal). Perfusion. 2023 Nov;38(8):1584-1599. doi: 10.1177/02676591221122350. Epub 2022 Aug 22.

PMID: 35994013BACKGROUND

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

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.

Sponsor Type

OTHER

Responsible Party

PRINCIPAL INVESTIGATOR

PI Title

Consultant in Cardiac Anesthesia

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

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (28)

Study Arms (2)

Placebo

Desmopressin

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (25)

Study Officials

Central Study Contacts

Study Design

Study Record Dates

You may not qualify if:

Data Sharing

Source record

Locations

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (28)

Study Arms (2)

Placebo

Desmopressin

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (25)

Study Officials

Central Study Contacts

Study Design

Study Record Dates

You may not qualify if:

Data Sharing

Source record

Locations