Dose for Reversal of Heparin After Cardiopulmonary Bypass

NCT07477977 | Recruiting

• 1 other identifier: Soh-Med-26-1-5PD
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 1

Brief Summary

Protamine sulfate is routinely used to reverse heparin anticoagulation after cardiopulmonary bypass (CPB). The conventional dosing strategy of 1 mg protamine per 100 IU of heparin may result in excess protamine exposure, which has been associated with anticoagulant effects, platelet dysfunction, and hemodynamic instability. Recent evidence suggests that lower protamine doses may provide adequate heparin reversal while reducing potential adverse effects.  This multicenter, prospective, randomized, double-blind, controlled trial aims to compare three protamine-to-heparin dosing ratios (1:1, 0.8:1, and 0.75:1) in adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. The primary outcome is activated clotting time (ACT) measured 5 minutes after protamine administration. Secondary outcomes include the need for additional protamine administration, protamine-related adverse events, postoperative bleeding, blood product transfusion requirements, and length of intensive care unit stay.  The results of this study may help determine whether reduced protamine dosing can safely achieve effective heparin reversal while minimizing drug exposure and potential complications after cardiopulmonary bypass. 

Conditions

Open Heart Surgery

Keywords

Protamine; Heparin; Activated clotting time; Postoperative bleeding; Cardiac surgery

Outcome Measures

Primary Outcomes (1)

• Post-protamine Activated Clotting Time (ACT)

  Activated clotting time measured 5 minutes after completion of protamine administration to assess adequacy of heparin reversal after cardiopulmonary bypass.

  5 minutes after protamine administration

Secondary Outcomes (5)

• Need for additional protamine administration

  5 minutes after initial protamine administration

• Postoperative chest tube drainage

  Within 24 hours after surgery

• Blood transfusion requirements

  Within 24 hours after surgery

• Protamine-related adverse events

  From protamine administration until 24 hours after surgery

• Re-exploration for bleeding

  Within 24 hours after surgery

Study Arms (3)

Standard Protamine Dose (1:1)

ACTIVE COMPARATOR

Participants will receive protamine sulfate at a ratio of 1 mg per 100 IU of the initial heparin dose administered during cardiopulmonary bypass. Protamine will be administered intravenously over 5-10 minutes at the termination of cardiopulmonary bypass for heparin reversal.

Drug: Protamine sulfate

Reduced Protamine Dose (0.8:1)

EXPERIMENTAL

Participants will receive protamine sulfate at a ratio of 0.8 mg per 100 IU of the initial heparin dose administered during cardiopulmonary bypass. Protamine will be administered intravenously over 5-10 minutes at the termination of cardiopulmonary bypass for heparin reversal.

Drug: Protamine sulfate

Reduced Protamine Dose (0.75:1)

EXPERIMENTAL

Participants will receive protamine sulfate at a ratio of 0.75 mg per 100 IU of the initial heparin dose administered during cardiopulmonary bypass. Protamine will be administered intravenously over 5-10 minutes at the termination of cardiopulmonary bypass for heparin reversal.

Drug: Protamine sulfate

Interventions

Protamine sulfate DRUG

Protamine sulfate will be administered intravenously for reversal of heparin anticoagulation after cardiopulmonary bypass. The dose will be calculated according to the randomized study group based on the initial heparin dose administered during cardiopulmonary bypass.

Also known as: Protamine

Reduced Protamine Dose (0.75:1); Reduced Protamine Dose (0.8:1); Standard Protamine Dose (1:1)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass (CABG, valve surgery, or combined procedures)
• Patients receiving systemic heparinization according to the institutional cardiopulmonary bypass protocol
• Ability to provide written informed consent before surgery

You may not qualify if:

• Known allergy or hypersensitivity to protamine
• Pre-existing coagulopathy or bleeding disorders
• Patients receiving chronic anticoagulation that cannot be safely discontinued before surgery
• Severe renal dysfunction
• Severe hepatic dysfunction
• Emergency cardiac surgery
• Pregnancy
• Off-pump cardiac surgery

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Sohag University Hospital

Sohag, Egypt

RECRUITING

MeSH Terms

Conditions

Postoperative Hemorrhage

Interventions

Protamines

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications

Intervention Hierarchy (Ancestors)

Nuclear Proteins; Proteins; Amino Acids, Peptides, and Proteins; Nucleoproteins

Study Officials

• Asmaa S Farghaly, MD

  Faculty of Medicine, Sohag University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asmaa S Farghaly, MD

CONTACT

+20 10 20283823; asmaasaad@med.sohag.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Protamine doses will be prepared by an unblinded perfusionist or pharmacist in indistinguishable syringes according to the randomized allocation. The surgical, anesthesia, and intensive care teams, as well as patients and outcome assessors, will remain blinded to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Anesthesia, Intensive Care and Pain Management. Faculty of Medicine

Model Details: Participants undergoing elective cardiac surgery with cardiopulmonary bypass will be randomized in a 1:1:1 allocation to receive one of three protamine-to-heparin dosing ratios (1:1, 0.8:1, or 0.75:1) at the termination of cardiopulmonary bypass.

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: March 17, 2026
• Study Start: March 1, 2026
• Primary Completion: June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Locations

EG (1)