HemodilutionPhase 3RAPPER-MANNCT04870073
Retrograde Autologous Priming and Mannitol for Reducing Hemodilution in Cardiac Surgery
A Phase 3 study testing Retrograde autologous priming, Mannitol and Conventional Priming in people with Hemodilution and Coronary Artery Disease, run by Hamilton Health Sciences Corporation at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodilution, Coronary Artery Disease, Fluid Overload
- What is being tested?
- Retrograde autologous priming, Mannitol and Conventional Priming
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- 21 Sep 2022to 21 Sep 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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.
Who cannot join
- 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)
Show all 12Show fewer
- Hemoglobin <80 g/L
- Thrombocytopenia (<50,000 platelets per μL)
- Expected circulatory arrest
- Body weight ≤50 kg
- Allergy to mannitol
- Pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hemodilution, Coronary Artery Disease, Fluid Overload
- Being tested
- Retrograde autologous priming, Mannitol, Conventional Priming
- Keywords
- retrograde autologous priming, mannitol, cardiopulmonary bypass, cardiac surgery, hemodilution
- Medical subject headings
- Coronary Artery Disease, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retrograde autologous primingProcedure or surgery
Also called RAP
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.
MannitolDrug
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 PrimingProcedure or surgery
The conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Mannitol; Procedure: Conventional Priming |
| Conventional priming alone | Active comparator | Participants will receive conventional priming alone. Receives: Procedure: Conventional Priming |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility Outcomes
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%.
Measured: 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
Measured: Start to end of cardiopulmonary bypass
Secondary outcomes (1)
Change in hemoglobin concentration after cardiopulmonary bypass
Change in arterial hemoglobin concentration from baseline to discharge
Measured: Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2021
- Study start21 Sep 2022
- Primary completion21 Sep 2022
- Study completion21 Sep 2022
Why it stopped: Financial support could not be obtained for the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HemodilutionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- single-centre, single blinded, 2x2 factorial, cluster randomized trial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University
- Responsible party
- Principal investigator, Andre Lamy, Hamilton Health Sciences Corporation
- Investigators
- Andre Lamy, MD, Principal investigator, Hamilton Health Sciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04870073
- Sponsor's protocol ID
- RAPPER-MAN_2021
- Acronym
- RAPPER-MAN
- Status last verified
- Feb 2023
- First submitted
- 20 Apr 2021
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32947294Ljunggren 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.
PubMed 31287556Task 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.
PubMed 29029990Trapp 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.
PubMed 25803120
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrograde Autologous Priming for Preserving Hemoglobin Peri-operatively With or Without Mannitol: A Pilot Study
- ClinicalTrials.gov ID
- NCT04870073
- Acronym / sponsor ID
- RAPPER-MAN / RAPPER-MAN_2021
- Conditions
- Hemodilution, Coronary Artery Disease, Fluid Overload
- Keywords
- retrograde autologous priming, mannitol, cardiopulmonary bypass, cardiac surgery, hemodilution
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Financial support could not be obtained for the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Collaborators
- McMaster University
- Study start
- 21 Sep 2022 (actual)
- Primary completion
- 21 Sep 2022 (actual)
- Study completion
- 21 Sep 2022 (actual)
- First posted
- 3 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- single-centre, single blinded, 2x2 factorial, cluster randomized trial
| Arm | Type | Receives |
|---|---|---|
| Retrograde autologous priming + mannitol | Experimental | Procedure: Retrograde autologous priming, Drug: MannitolPriming 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 | Experimental | Procedure: Retrograde autologous primingPriming 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 | Experimental | Drug: Mannitol, Procedure: Conventional PrimingParticipants 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 | Active comparator | Procedure: Conventional PrimingParticipants will receive conventional priming alone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- ≥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.
Key exclusion criteria (12 listed)
- Left ventricle ejection fraction <25%
- Emergency surgery
- History of bleeding disorder
- Inherited thromboembolic or infective endocarditis (active)
- Previous cardiac surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retrograde autologous primingAlso: RAPPriming 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 or surgery | Retrograde autologous priming + mannitol, Retrograde autologous priming alone |
| MannitolMannitol 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 | Conventional priming + mannitol, Retrograde autologous priming + mannitol |
| Conventional PrimingThe conventional priming procedure will be used in the standardized cardiopulmonary machine used at the Hamilton General Hospital. | Procedure or surgery | Conventional priming + mannitol, Conventional priming alone |
Primary outcome
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: 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
Time frame: Start to end of cardiopulmonary bypass
Change in arterial hemoglobin concentration during cardiopulmonary bypass
1 secondary outcome
Change in hemoglobin concentration after cardiopulmonary bypass
Time frame: Start of cardiopulmonary bypass to hospital discharge or 5 days maximum (whichever occurs first)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Background: PubMed 32947294Hensley 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.
- Background: PubMed 31287556Ljunggren 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.
- Background: PubMed 29029990Task 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.
- Background: PubMed 25803120Trapp 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andre Lamy, MD principal investigator
Hamilton Health Sciences Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Retrograde autologous priming, Mannitol and Conventional Priming in people with Hemodilution and Coronary Artery Disease, run by Hamilton Health Sciences Corporation at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility Outcomes (time frame: Start to end of study recruitment, which is anticipated to take 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04870073, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.