PrOtamIne doSing clOt imagiNg (POISON) Study (POISON)

Scanning Electron Microscopy (SEM) and Confocal Imaging of Clot in Two Different Protamine Environments (PrOtamIne doSing clOt imagiNg (POISON) Study)

The proposed study involves using two different high-resolution microscopic imaging techniques to examine the health and platelet invasion of clot in patients who were given 1:1 protamine / heparin and compare this to clot from patients who had heparin reversed using the PRODOSE algorithm. Patients will be treated according to the routine clinical practice of their individual care team.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Surgery

Detailed Description

Sample collection at RPH

Patients will have a total of 14ml of blood taken during the procedure.

The first 7ml will be taken after induction of anaesthesia along with routine blood gas and coagulation sampling through the routinely indwelling arterial catheter. The initial sample must be taken before any heparin has been administered. This will be used to fill 2 x 3.5ml citrated (green top) blood tubes. These will be clearly labelled as "pre-heparin" with a Tissue Bank ID number.

The second 7ml will be taken 5 minutes after heparin has been reversed with protamine after cessation of cardiopulmonary bypass. It will again be taken at the same time as routine sampling for blood gas and coagulation studies. Analog to the first sample, it will again be divided and used to fill 2 x 3.5ml citrated (green top) blood tubes. These will be clearly labelled as "post-protamine" with the same ID number and whether "1:1" or a "PRODOSE algorithm determined" protamine: heparin ratio was used.

In keeping with clinical routine, ROTEM coagulation testing and full blood counts will be requested as seen necessary by the clinical team.

The samples will be sent to Royal Papworth Hospital (RPH) Tissue Bank for initial processing. Samples need to be processed within 4 hours of blood draw.

After initial processing, samples will be sent for confocal imaging to the MRC Laboratory of Molecular Biology (LMB) and for SEM imaging to the University of Oxford respectively.

Clinical data to be collected (to be completed by anaesthetic team).

1. Demographic information: Age / Gender / Weight / Height / Medication history;
2. Type of surgery;
3. Cardiac drug history and antiplatelets / anticoagulants and timing;
4. Coagulation tests (ACT / ROTEM) at the following points: a) Pre-heparin, b) Post-heparin, pre-CPB, c) Throughout CPB, c) Post-protamine;
5. Full blood count at the following points: a) Pre-surgery and date of sample, b) Post-protamine; 6) CPB and x-clamp times, nadir temperature

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Royal Papworth Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing elective, uncomplicated single procedure cardiac surgery with anticipated CPB duration < 120 min

Description

Inclusion Criteria:

• undergoing elective, uncomplicated single procedure cardiac surgery with anticipated CPB duration < 120 min
• with all anticoagulant drugs stopped at least 5 days before surgery, apart from aspirin
• with normal full blood count and clotting screen pre-OP.

Exclusion Criteria:

• emergency surgery
• inability to stop anticoagulants except aspirin for 5 days pre-OP
• complex surgery with anticipated CPB duration > 120min
• operations planned to be done at temperature on CPB < 34 degrees
• operations requiring deep hypothermic circulatory arrest, solid organ transplantation
• know blood dyscrasia
• intra-operative blood or blood product transfusion or post-operative coagulopathy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Standard; 10 patients receiving standard reversal with 1:1 protamine / heparin ratio
PRODOSE Algorithm; 10 patients who had heparin reversed using the PRODOSE algorithm anticipated (average protamine / heparin ratio 0.6:1).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-resolution microscopic images (Scanning Electron Microscopy and Confocal Imaging)	The proposed study involves using two different high-resolution microscopic imaging techniques to examine the health and platelet invasion of clot in patients who were given 1:1 protamine / heparin and compare this to clot from patients who had heparin reversed using the PRODOSE algorithm. This is an observational study in which differences between images of clot obtained from samples from the two patient groups and before and after cardiopulmonary bypass will be described.	Pre Heparin and Post Protamine [5 minutes after heparin has been reversed]

Collaborators and Investigators

• Sponsor: Papworth Hospital NHS Foundation Trust
• Collaborators: Medical Research Council; University of Oxford; University of Liverpool

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 8, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 21, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: T03024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Small observational study so IPD not relevant

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No