Clinical trial NCT04870073: Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery
Official title: Retrograde Autologous Priming for Preserving Hemoglobin Peri-operatively With or Without Mannitol: A Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hemodilution
Coronary Artery Disease
Fluid Overload
Keywords: retrograde autologous priming
mannitol
cardiopulmonary bypass
cardiac surgery
hemodilution
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2021-05-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: single-centre, single blinded, 2x2 factorial, cluster randomized trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility Outcomes
timeFrame: Start to end of study recruitment, which is anticipated to take 20 weeks
measure: Change in hemoglobin concentration during cardiopulmonary bypass
timeFrame: Start to end of cardiopulmonary bypass
Secondary outcomes:
measure: Change in hemoglobin concentration after cardiopulmonary bypass
timeFrame: Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)
Other outcomes:
measure: Blood transfusion
timeFrame: Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
measure: Change in oxygen consumption during cardiopulmonary bypass
timeFrame: Start to end of cardiopulmonary bypass
measure: Autologous prime volume
timeFrame: Within 10 minutes before cardiopulmonary bypass
measure: Hyponatremia
timeFrame: Before and 24 hours after surgery
measure: Diuresis
timeFrame: Within 24 hours of surgery
measure: Hemofiltration use
timeFrame: During cardiopulmonary bypass
measure: Fluid balance
timeFrame: Daily in ICU from admission to hospital discharge or 5 days maximum (whichever occurs first)
measure: Acute kidney injury
timeFrame: Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
measure: Length of hospital stay
timeFrame: Time from admission to hospital discharge or 5 days maximum (whichever occurs first)
measure: Major adverse cardiovascular events
timeFrame: Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Andre Lamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.