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Hypovolemic Phlebotomy to Reduce Blood Transfusions in Major Hepatic Resections (PRICE2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03651154
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : August 18, 2020
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Brief Summary:
Major liver resection is associated with substantial intraoperative blood loss and subsequently blood transfusions. Blood transfusion in elective liver surgery is a significant factor of perioperative morbidity and mortality, as well as possibly long-term oncologic outcome. The purpose of this study is to use whole blood phlebotomy to decrease the central venous pressure, resulting in a state of relative hypovolemia. It is hypothesized that this intervention will lead to a decrease in blood loss at the time of liver resection and thus reduced blood transfusion in major liver surgeries.

Condition or disease Intervention/treatment Phase
Liver Neoplasms Hepatectomy Blood Transfusion Blood Loss, Surgical Procedure: Hypovolemic Phlebotomy Not Applicable

Detailed Description:
Major liver resection is associated with significant intraoperative blood loss and blood transfusions. Blood transfusion in elective liver surgery is a key determinant of perioperative morbidity and mortality, as well as possibly long-term oncologic outcome. Whole blood phlebotomy is a simple intervention, whose aim is to decrease the central venous pressure yielding a state of relative hypovolemia and thus lead to decreased blood loss and subsequently blood transfusion. Small studies, mostly from the liver transplant literature, would suggest that phlebotomy with controlled hypovolemia can result in decreased blood loss and blood transfusion. Since blood loss is an important issue in liver surgery, and the benefits of phlebotomy and controlled hypovolemia are unknown in liver resection patients, a rigorously conducted trial in a representative population of patients undergoing liver resection is warranted, and feasible. In this proposal, it is hypothesized that by the use of hypovolemic phlebotomy, it is possible to decrease blood loss and blood transfusions. To test this hypothesis the investigators plan to randomly allocate participants to hypovolemic phlebotomy plus standard of care or to standard of care. Participants will be those patients undergoing elective major liver resection at The Ottawa Hospital, le Centre Hospitalier de l'Université de Montréal, and le Centre Hospitalier de l'Université de Sherbrooke for any indication. The primary outcome will be red blood cells transfusion up to 30 days following surgery. Secondary outcomes will include intraoperative blood loss, other blood product transfusion requirements, perioperative morbidity and mortality, safety, physiologic parameters, and feasibility elements. A total of 440 patients will be randomized across the 3 sites in Ontario and Quebec. The efficacy of phlebotomy in terms of blood loss and transfusion prevention will be assessed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PRICE 2: A Phase 3 Randomized Controlled Trial of Phlebotomy Resulting in Controlled Hypovolemia to Prevent Blood Loss in Major Hepatic Resections
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Hypovolemic Phlebotomy

Hypovolemic Phlebotomy will consist of the withdrawal of 7-10 mL/kg of whole blood from the patient, as tolerated (e.g. for a 70kg patient, 490 to 700 mL of whole blood will be removed) The volume of removed blood will not be replaced by the administration of intravenous fluids.

Removed blood will be transfused back to participant at the end of surgery. The phlebotomized whole blood will be transfused back after liver transection regardless of blood loss.

Procedure: Hypovolemic Phlebotomy
Removal of 7-10ml/kg of blood from participant, as tolerated after patient is under anesthesia, before liver resection start time

No Intervention: Control (Standard of Care)
Standard of care (low CVP surgery). In this arm, standard anesthesia will be maintained.



Primary Outcome Measures :
  1. Packed Red Blood Cell Transfusion Rates [ Time Frame: 30 days post-operation ]
    Units of packed red blood cells transfused to participants


Secondary Outcome Measures :
  1. Blood product transfusion rates [ Time Frame: Postoperative setting up to 30 days following surgery ]
    Types and amount of other blood product transfusion rates in the 30 day period following surgery.

  2. Intraoperative blood loss [ Time Frame: up to 90 days before surgery; and on post-operative day 2 ]
    Intraoperative blood loss is notoriously difficult to measure. It is suggested that calculation of blood loss using preoperative and postoperative hemoglobin levels in most consistently accurate. In order to minimize the risk of bias associated with any one method of intraoperative measurement of blood loss, three methods will be used independently. In the operating room, all blood and fluid aspirated from the abdomen will be measured accurately using graduated suction containers. As well, the amount of irrigation fluid will be carefully monitored and recorded. Finally, the weight of all surgical sponges will be measured. This information will be used by the surgeon and anesthesiologist to independently visually estimate blood loss, as is commonly done in clinical practice. In parallel, intraoperative blood loss will also be calculated based on an equation.

  3. Perioperative morbidity and mortality [ Time Frame: Postoperative setting up to 30 days following surgery ]
    Perioperative morbidity is assessed using the Dindo-Clavien scale and is defined as any deviation from the normal post-operative course. The scale (1-5) indicates the severity of an adverse event; where 1 is low (i.e. "any deviation from normal postoperative course without the need for intervention") and 5 means death of the patient (i.e. mortality).

  4. Changes in physiologic parameters (Central Venous Pressure) [ Time Frame: measured during surgery (intraoperatively) ]
    Central venous pressure (CVP) is a physiologic parameter that measures the blood pressure in the thoracic vena cava (in cm H20)

  5. Changes in physiologic parameters (Pulse Pressure Variation) [ Time Frame: measured during surgery (intraoperatively) ]
    Pulse Pressure variation (in %) is a predictor of fluid responsiveness



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients (≥18 years)
  • projected to undergo a major liver resection (≥3 segments resected or partially resected), a right posterior sectionectomy (segments 6/7), or central resection (4b/5) for any indication, or the resection of 1 or more segments in a known cirrhotic patient.

Exclusion Criteria:

  • Age <18 years
  • Preoperative hemoglobin <100g/L
  • GFR clearance <60mL/min
  • Abnormal coagulation parameters (not on warfarin and/or platelets count <100 X10^9/L)
  • Evidence of hepatic metabolic disorder
  • Active cardiac conditions: Unstable coronary syndromes; Severe valvular disease; and Myocardial infarction within 6 months prior to surgery
  • History of significant cerebrovascular disease: Patients with clinically-significant stroke/CVA within the past 6 months or severe carotid stenosis (defined as >70%)
  • History of significant peripheral vascular disease: Non-revascularized with regular/ongoing claudication
  • Pregnancy
  • Refusal of blood products
  • Presence of active infection
  • Preoperative autologous blood donation
  • Planned intraoperative use of cell saver

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03651154


Contacts
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Contact: Aklile Workneh, MSc 6137378899 ext 71484 aworkneh@ohri.ca

Locations
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Canada, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Guillaume Martel, MD, MSc, FRCSC, FACS    6137378899 ext 71053    gumartel@toh.ca   
Contact: Aklile Workneh, MSc    6137378899 ext 71484    aworkneh@ohri.ca   
Principal Investigator: Guillaume Martel, MD, MSc, FRCSC, FACS         
Canada, Quebec
Centre Hospitalier de l"Université de Sherbrooke Recruiting
Montréal, Quebec, Canada
Contact: Yves Collins, MD         
Centre Hospitalier de l'Université de Montréal Recruiting
Montréal, Quebec, Canada
Contact: François Carrier, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
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Principal Investigator: Guillaume Martel, MD, MSc, FRCSC, FACS Ottawa Hospital Research Institute
Publications:

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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT03651154    
Other Study ID Numbers: 502
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Neoplasms
Hemorrhage
Blood Loss, Surgical
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Intraoperative Complications