Algorithmic Protamine Dosing for Reversal of Heparin After Cardiopulmonary Bypass

NCT03532594 | Completed

• 1 other identifier: P02337
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 1

Brief Summary

The PRODOSE trial is investigating a bespoke pharmacokinetic algorithm that calculates a tailored dose of protamine, required after cardiopulmonary bypass to reverse the action of heparin, based on individual patients and their actual bypass time. The PRODOSE trial aims to demonstrate that the algorithm can be used to define a protamine dose that will more reliably return coagulation parameters to pre-heparin levels as well as decreasing the risk of post-operative bleeding and transfusion. The trial aims to recruit 200 patients who will be randomised to either a bespoke or standard dose of protamine. The randomisation ratio will be 1:1 in the first instance but the trial uses an adaptive design and an interim analysis will be conducted after 100 patients have been randomised. The randomisation ratio could then be updated after the interim analysis to favour a superior arm whilst preserving statistical power levels.

Conditions

Heart Diseases; Cardiovascular Diseases

Keywords

Protamine; Heparin Antagonists; Cardiopulmonary Bypass

Outcome Measures

Primary Outcomes (1)

• Return to normal coagulation after cessation of cardiopulmonary bypass and reversal of heparin

  Kaolin Thrombelastography (TEG) r-time

  3 minutes post-protamine administration after cessation of cardiopulmonary bypass.

Secondary Outcomes (2)

• Blood loss

  4 hours post-surgery

• Blood products usage

  24 hours post-surgery

Study Arms (2)

Standard Care

OTHER

At the conclusion of cardiopulmonary bypass, protamine administration will be undertaken at surgical request. For patients in the control group, protamine will be dosed on a 1:1 ratio according to the total dose of heparin initially required to establish a therapeutic activated clotting time (ACT) (i.e. if 30,000 IU were required prior to initiating cardiopulmonary bypass, then the protamine dose will be 300mg).

Procedure: Standard Care

Algorithm

EXPERIMENTAL

For patients in the intervention group, protamine will be administered according to the PRODOSE algorithm, which has been incorporated into an Excel spread sheet for ease of use (Microsoft Corporation).

Procedure: PRODOSE Algorithm

Interventions

PRODOSE Algorithm PROCEDURE

Protamine administered according to PRODOSE algorithm

Algorithm

Standard Care PROCEDURE

Protamine administered according to Standard Care

Standard Care

Eligibility Criteria

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

You may qualify if:

• \* Patients scheduled to undergo elective cardiac surgery

You may not qualify if:

• Emergency surgery
• Age \< 18 years
• Known or suspected coagulopathy or platelet dysfunction
• Adenosine diphosphate (ADP)-receptor antagonists within 7 days of surgery (clopidogrel, ticlopidine, prasugrel)
• Total body weight \> 130kg
• End stage renal failure requiring dialysis
• Plan for severe hypothermia (\< 28°C) or deep hypothermic circulatory arrest
• Complex cardiac surgery (redo sternotomy, surgery on the thoracic aorta \[excluding root\])
• Transplantation

Sponsors & Collaborators

• Papworth Hospital NHS Foundation Trust: lead
• Austin Health: collaborator

Study Sites (1)

Royal Papworth Hospital NHS Foundation Trust

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

Location

Related Publications (1)

• Miles LF, Burt C, Arrowsmith J, McKie MA, Villar SS, Govender P, Shaylor R, Tan Z, De Silva R, Falter F. Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial. PLoS Med. 2021 Jun 7;18(6):e1003658. doi: 10.1371/journal.pmed.1003658. eCollection 2021 Jun.

  PMID: 34097705 DERIVED

MeSH Terms

Conditions

Heart Diseases; Cardiovascular Diseases

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Florian Falter, FRCA

  Royal Papworth Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Lachlan Miles, FRCA

  Austin Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: The randomisation ratio will be 1:1 in the first instance but the trial uses an adaptive design and an interim analysis will be conducted after 100 patients have been randomised.

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: May 22, 2018
• Study Start: April 16, 2018
• Primary Completion: October 30, 2019
• Study Completion: January 30, 2020
• Last Updated: June 23, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)