Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery

NCT04870073 | Withdrawn Phase 3

• 1 other identifier: RAPPER-MAN_2021
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemodilution; Coronary Artery Disease; Fluid Overload

Keywords

retrograde autologous priming; mannitol; cardiopulmonary bypass; cardiac surgery; hemodilution

Outcome Measures

Primary Outcomes (2)

• Feasibility Outcomes

  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%.

  Start to end of study recruitment, which is anticipated to take 20 weeks

• Change in hemoglobin concentration during cardiopulmonary bypass

  Change in arterial hemoglobin concentration during cardiopulmonary bypass

  Start to end of cardiopulmonary bypass

Secondary Outcomes (1)

• Change in hemoglobin concentration after cardiopulmonary bypass

  Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)

Other Outcomes (10)

• Blood transfusion

  Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)

• Change in oxygen consumption during cardiopulmonary bypass

  Start to end of cardiopulmonary bypass

• Autologous prime volume

  Within 10 minutes before cardiopulmonary bypass

Study Arms (4)

Retrograde autologous priming + mannitol

EXPERIMENTAL

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; Drug: Mannitol

Retrograde autologous priming alone

EXPERIMENTAL

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

Conventional priming + mannitol

EXPERIMENTAL

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; Procedure: Conventional Priming

Conventional priming alone

ACTIVE COMPARATOR

Participants will receive conventional priming alone.

Procedure: Conventional Priming

Interventions

Retrograde autologous priming PROCEDURE

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.

Also known as: RAP

Retrograde autologous priming + mannitol; Retrograde autologous priming alone

Mannitol DRUG

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; Retrograde autologous priming + mannitol

Conventional Priming PROCEDURE

The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.

Conventional priming + mannitol; Conventional priming alone

Eligibility Criteria

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

You may qualify if:

• ≥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.

You may not qualify if:

• Left ventricle ejection fraction \<25%
• Emergency surgery
• History of bleeding disorder
• Inherited thromboembolic or infective endocarditis (active)
• Previous cardiac surgery
• Severe renal impairment (serum creatinine \>250 μmol/L)
• Hemoglobin \<80 g/L
• Thrombocytopenia (\<50,000 platelets per μL)
• Expected circulatory arrest
• Body weight ≤50 kg
• Allergy to mannitol
• Pregnancy or breast feeding

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• McMaster University: collaborator

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (4)

• Hensley NB, Gyi R, Zorrilla-Vaca A, Choi CW, Lawton JS, Brown CH 4th, Frank SM, Grant MC, Cho BC. Retrograde Autologous Priming in Cardiac Surgery: Results From a Systematic Review and Meta-analysis. Anesth Analg. 2021 Jan;132(1):100-107. doi: 10.1213/ANE.0000000000005151.

  PMID: 32947294 BACKGROUND

• Ljunggren M, Skold A, Dardashti A, Hyllen S. The use of mannitol in cardiopulmonary bypass prime solution-Prospective randomized double-blind clinical trial. Acta Anaesthesiol Scand. 2019 Nov;63(10):1298-1305. doi: 10.1111/aas.13445. Epub 2019 Jul 29.

  PMID: 31287556 BACKGROUND

• Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Cardiothoracic Anaesthesiology (EACTA); Boer C, Meesters MI, Milojevic M, Benedetto U, Bolliger D, von Heymann C, Jeppsson A, Koster A, Osnabrugge RL, Ranucci M, Ravn HB, Vonk ABA, Wahba A, Pagano D. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. J Cardiothorac Vasc Anesth. 2018 Feb;32(1):88-120. doi: 10.1053/j.jvca.2017.06.026. Epub 2017 Sep 30. No abstract available.

  PMID: 29029990 BACKGROUND

• Trapp C, Schiller W, Mellert F, Halbe M, Lorenzen H, Welz A, Probst C. Retrograde Autologous Priming as a Safe and Easy Method to Reduce Hemodilution and Transfusion Requirements during Cardiac Surgery. Thorac Cardiovasc Surg. 2015 Oct;63(7):628-34. doi: 10.1055/s-0035-1548731. Epub 2015 Mar 24.

  PMID: 25803120 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Edema

Interventions

Mannitol

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Andre Lamy, MD

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiac Surgeon

Model Details: single-centre, single blinded, 2x2 factorial, cluster randomized trial

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: May 3, 2021
• Study Start: September 21, 2022
• Primary Completion: September 21, 2022
• Study Completion: September 21, 2022
• Last Updated: February 28, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)