- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04870073
Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery (RAPPER-MAN)
February 27, 2023 updated by: Andre Lamy, Hamilton Health Sciences Corporation
Retrograde Autologous Priming for Preserving Hemoglobin Peri-operatively With or Without Mannitol: A Pilot Study
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.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
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 Type
Interventional
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Austin Browne, PhD
- Phone Number: 40582 19052973479
- Email: Austin.Browne@phri.ca
Study Contact Backup
- Name: Andre Lamy, MD
- Email: lamya@mcmaster.ca
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8L 2X2
- Hamilton General Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Single
Arms and Interventions
Participant Group / 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.
|
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:
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.
|
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:
|
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.
|
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.
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.
|
The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility Outcomes
Time Frame: 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:
|
Start to end of study recruitment, which is anticipated to take 20 weeks
|
Change in hemoglobin concentration during cardiopulmonary bypass
Time Frame: Start to end of cardiopulmonary bypass
|
Change in arterial hemoglobin concentration during cardiopulmonary bypass
|
Start to end of cardiopulmonary bypass
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in hemoglobin concentration after cardiopulmonary bypass
Time Frame: Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)
|
Change in arterial hemoglobin concentration from baseline to discharge
|
Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood transfusion
Time Frame: Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
|
Proportion of patients experiencing red blood cell transfusion
|
Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
|
Change in oxygen consumption during cardiopulmonary bypass
Time Frame: Start to end of cardiopulmonary bypass
|
Change in oxygen consumption during cardiopulmonary bypass
|
Start to end of cardiopulmonary bypass
|
Autologous prime volume
Time Frame: Within 10 minutes before cardiopulmonary bypass
|
Total prime volume removed from the extracorporeal circuit during the retrograde autologous priming procedure
|
Within 10 minutes before cardiopulmonary bypass
|
Hyponatremia
Time Frame: Before and 24 hours after surgery
|
Sodium concentration of less than 135 mmol/L (135 mEq/L)
|
Before and 24 hours after surgery
|
Diuresis
Time Frame: Within 24 hours of surgery
|
Total volume of urine within 24 hours of surgery
|
Within 24 hours of surgery
|
Hemofiltration use
Time Frame: During cardiopulmonary bypass
|
Proportion of patients undergoing hemofiltration
|
During cardiopulmonary bypass
|
Fluid balance
Time Frame: 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
|
Daily in ICU from admission to hospital discharge or 5 days maximum (whichever occurs first)
|
Acute kidney injury
Time Frame: Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
|
Acute kidney injury as measured by peak postoperative creatinine and KDIGO
|
Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
|
Length of hospital stay
Time Frame: Time from admission to hospital discharge or 5 days maximum (whichever occurs first)
|
Length of hospital stay (days)
|
Time from admission to hospital discharge or 5 days maximum (whichever occurs first)
|
Major adverse cardiovascular events
Time Frame: Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
|
Composite outcome of cardiovascular death, non-fatal myocardial infarction or stroke
|
Start of surgery to hospital discharge or 5 days maximum (whichever occurs first)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Andre Lamy, MD, Hamilton Health Sciences Corporation
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 21, 2022
Primary Completion (Actual)
September 21, 2022
Study Completion (Actual)
September 21, 2022
Study Registration Dates
First Submitted
April 20, 2021
First Submitted That Met QC Criteria
April 29, 2021
First Posted (Actual)
May 3, 2021
Study Record Updates
Last Update Posted (Estimate)
February 28, 2023
Last Update Submitted That Met QC Criteria
February 27, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RAPPER-MAN_2021
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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