RAPPER-MAN: Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery

Sponsor

Hamilton Health Sciences Corporation (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04870073

Collaborator

McMaster University (Other)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

18.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hemodilution Coronary Artery Disease Fluid Overload	Procedure: Retrograde autologous priming Drug: Mannitol Procedure: Conventional Priming	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

single-centre, single blinded, 2x2 factorial, cluster randomized trialsingle-centre, single blinded, 2x2 factorial, cluster randomized trial

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Retrograde Autologous Priming for Preserving Hemoglobin Peri-operatively With or Without Mannitol: A Pilot Study

Anticipated Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Feb 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Retrograde autologous priming + 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.	Procedure: 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. Other Names: RAP Drug: Mannitol 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.
Experimental: Retrograde autologous priming alone 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.	Procedure: 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. Other Names: RAP
Experimental: Conventional priming + 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.	Drug: Mannitol 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. Procedure: Conventional Priming The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.
Active Comparator: Conventional priming alone Participants will receive conventional priming alone.	Procedure: Conventional Priming The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.

Outcome Measures

Primary Outcome Measures

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: Average recruitment rate of 7 patients per week. Complete Hb data before and after cardiopulmonary bypass in 90% of patients. 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

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

Other Outcome Measures

Blood transfusion [Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)]
Proportion of patients experiencing red blood cell transfusion
Change in oxygen consumption during cardiopulmonary bypass [Start to end of cardiopulmonary bypass]
Change in oxygen consumption during cardiopulmonary bypass
Autologous prime volume [Within 10 minutes before cardiopulmonary bypass]
Total prime volume removed from the extracorporeal circuit during the retrograde autologous priming procedure
Hyponatremia [Before and 24 hours after surgery]
Sodium concentration of less than 135 mmol/L (135 mEq/L)
Diuresis [Within 24 hours of surgery]
Total volume of urine within 24 hours of surgery
Hemofiltration use [During cardiopulmonary bypass]
Proportion of patients undergoing hemofiltration
Fluid balance [Daily in ICU from admission to hospital discharge or 5 days maximum (whichever occurs first)]
Net fluid balance (intake minus output) calculated using a cumulative fluid chart
Acute kidney injury [Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)]
Acute kidney injury as measured by peak postoperative creatinine and KDIGO
Length of hospital stay [Time from admission to hospital discharge or 5 days maximum (whichever occurs first)]
Length of hospital stay (days)
Major adverse cardiovascular events [Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)]
Composite outcome of cardiovascular death, non-fatal myocardial infarction or stroke

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥18 years of age.
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.