Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery

Phase 3

Withdrawn

• Conditions: Coronary Artery Disease; Fluid Overload; Hemodilution
• Interventions: Procedure: Retrograde autologous priming; Drug: Mannitol; Procedure: Conventional Priming

• Registration Number: NCT04870073
• Lead Sponsor: Hamilton Health Sciences Corporation

Brief Summary

Hemodilution reduces concentrations of blood constituents: concentration of hemoglobin, red blood cells (hematocrit), physiological ions and coagulation factors that can contribute to impaired hemostasis and increasing the risk of perioperative blood transfusions. This pilot study will assess the feasibility of a large RCT to evaluate 2 techniques for reducing hemodilution during cardiac surgery: 1) retrograde autologous priming and 2) intraoperative mannitol. The aim of this pilot trial is to demonstrate feasibility of a larger trial to evaluate whether retrograde autologous priming and/or mannitol are superior to conventional priming alone.

Detailed Description

The use of large volumes of artificial priming fluids is still very high in cardiac surgery for routine CABG surgery with cardiopulmonary bypass. The resulting hemodilution is deleterious for patients and often requires counter measures to maintain fluid balance during and after surgery. Retrograde autologous priming and mannitol are simple low-cost solutions to the problem of hemodilution but their effectiveness, either alone or in combination, is unclear due to a lack of high-quality evidence. RAPPER-MAN is a single-centre 2x2 factorial cluster randomized trial. Participants will be randomly assigned (1:1:1:1 ratio) to the intervention groups: 1) Retrograde autologous priming (≥600 mL) + mannitol (0.3 g/kg bolus), 2) Retrograde autologous priming (≥600 mL) alone, 3) Conventional priming + mannitol (0.3 g/kg bolus), and 4) Conventional priming alone. The primary outcome is the change in hemoglobin concentration during cardiopulmonary bypass. Retrograde autologous priming will be performed within 10 minutes before, and mannitol will be added to the venous reservoir of the CPB machine within 5 minutes before, the start of cardiopulmonary bypass. The results of the larger trial are expected to have broad implications for fluid management in cardiac surgery in Canada.

Study Timeline

• Study First Submitted: 2021-04-20
• Study First Submitted QC: 2021-04-29
• Study First Posted: 2021-05-03
• Study Start: 2022-09-21
• Primary Completion: 2022-09-21
• Study Completion: 2022-09-21
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-27
• Last Update Posted: 2023-02-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. ≥18 years of age.
2. Undergoing a first-time cardiac surgical procedure (i.e. isolated CABG, isolated single cardiac valve surgery or a combination of both or isolated ascending aorta replacement) with the use of cardiopulmonary bypass (CPB) and median sternotomy.

Exclusion Criteria

1. Left ventricle ejection fraction <25%
2. Emergency surgery
3. History of bleeding disorder
4. Inherited thromboembolic or infective endocarditis (active)
5. Previous cardiac surgery
6. Severe renal impairment (serum creatinine >250 μmol/L)
7. Hemoglobin <80 g/L
8. Thrombocytopenia (<50,000 platelets per μL)
9. Expected circulatory arrest
10. Body weight ≤50 kg
11. Allergy to mannitol
12. Pregnancy or breast feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Retrograde autologous priming + mannitol	Retrograde autologous priming	Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team. In addition, mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass.
Retrograde autologous priming alone	Retrograde autologous priming	Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team.
Conventional priming + mannitol	Mannitol	Participants will receive conventional priming. In addition, mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass.
Conventional priming + mannitol	Conventional Priming	Participants will receive conventional priming. In addition, mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass.
Conventional priming alone	Conventional Priming	Participants will receive conventional priming alone.
Retrograde autologous priming + mannitol	Mannitol	Priming solution (≥600 mL) will be removed from the extracorporeal circuit within 10 minutes before the initiation of cardiopulmonary bypass. Priming solution may be removed from 3 locations within the extracorporeal circuit (i.e. arterial, venous and cardioplegia lines) as determined by the perfusionist team. In addition, mannitol will be added as a bolus (0.3 g/kg) to the venous reservoir of the cardiopulmonary bypass machine within 5 min before the start of cardiopulmonary bypass.

Primary Outcome Measures

Name	Time	Method
Feasibility Outcomes	Start to end of study recruitment, which is anticipated to take 20 weeks	Feasibility will be established in the pilot phase if all the following criteria are met: 1. Average recruitment rate of 7 patients per week.; 2. Complete Hb data before and after cardiopulmonary bypass in 90% of patients.; 3. Compliance of the research team members, OR staff and ward medical staff with the protocol of 90%.
Change in hemoglobin concentration during cardiopulmonary bypass	Start to end of cardiopulmonary bypass	Change in arterial hemoglobin concentration during cardiopulmonary bypass

Secondary Outcome Measures

Name	Time	Method
Change in hemoglobin concentration after cardiopulmonary bypass	Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)	Change in arterial hemoglobin concentration from baseline to discharge

Trial Locations

Locations (1)

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada