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

March 22, 2023 updated by: Ottawa Hospital Research Institute

PRICE 2: A Phase 3 Randomized Controlled Trial of Phlebotomy Resulting in Controlled Hypovolemia to Prevent Blood Loss in Major Hepatic Resections

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

440

Phase

  • Not Applicable

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: Aklile Workneh, MSc
  • Phone Number: 71484 6137378899
  • Email: aworkneh@ohri.ca

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
        • Vancouver General Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital
    • Quebec
      • Montréal, Quebec, Canada
        • Centre Hospitalier de l'Université de Montréal
      • Montréal, Quebec, Canada
        • Centre Hospitalier de l"Université de Sherbrooke

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:

  • 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

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Packed Red Blood Cell Transfusion Rates
Time Frame: 30 days post-operation
Units of packed red blood cells transfused to participants
30 days post-operation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Postoperative setting up to 30 days following surgery
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.
up to 90 days before surgery; and on post-operative day 2
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).
Postoperative setting up to 30 days following surgery
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)
measured during surgery (intraoperatively)
Changes in physiologic parameters (Pulse Pressure Variation)
Time Frame: measured during surgery (intraoperatively)
Pulse Pressure variation (in %) is a predictor of fluid responsiveness
measured during surgery (intraoperatively)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Hospital Research Institute

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

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 28, 2018

Primary Completion (Anticipated)

July 1, 2023

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

July 6, 2018

First Submitted That Met QC Criteria

August 27, 2018

First Posted (Actual)

August 29, 2018

Study Record Updates

Last Update Posted (Actual)

March 24, 2023

Last Update Submitted That Met QC Criteria

March 22, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 502

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Upon reasonable request, ethics approval and protocol approval from steering committee

IPD Sharing Time Frame

Upon request during analysis

IPD Sharing Access Criteria

Upon reasonable request, ethics approval and protocol approval from steering committee

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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