Clinical trial NCT02548910: Phlebotomy to Prevent Blood Loss in Major Hepatic Resections
Official title: The PRICE Trial: Phlebotomy Resulting in Controlled Hypovolemia to Prevent Blood Loss in Major Hepatic Resections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Neoplasms
Hepatectomy
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2015-09-14
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Major liver resection is associated with substantial intraoperative blood loss. Blood loss 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.

Detailed description: Major liver resection is associated with significant intraoperative blood loss. Blood loss 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. 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 phlebotomy and controlled hypovolemia, it is possible to decrease blood loss and blood transfusions. To test this hypothesis the investigators plan to randomly allocate participants to phlebotomy plus standard of care or to standard of care. Participants will be those patients undergoing elective major liver resection at the Ottawa Hospital for any indication. The primary outcome will be intraoperative blood loss. Secondary outcomes will include transfusion requirements, perioperative morbidity and mortality, safety, physiologic parameters, and feasibility elements. A total of 62 patients will be randomized. The efficacy of phlebotomy in terms of blood loss prevention will be assessed.

Eligibility criteria: Inclusion Criteria:

* Any patient being considered for a major elective liver resection will be considered for trial enrollment. Patients who are undergoing a concurrent additional abdominal or thoracic procedure (eg. colonic resection) will also be included.

Exclusion Criteria:

* Age \<18 years
* Pregnancy
* Refusal of blood products
* Active cardiac conditions: unstable coronary syndromes, decompensated heart failure (NYHA functional class IV; worsening or new-onset heart failure), significant arrhythmias, severe valvular disease
* History of significant cerebrovascular disease
* Renal dysfunction (patients with an estimated GFR \<60 mL/min)
* Abnormal coagulation parameters (INR \>1.5 not on warfarin and/or platelets count \<100 X109/L )
* Evidence of hepatic metabolic disorder (bilirubin \>35 umol/L)
* Presence of active infection
* Preoperative autologous blood donation
* Hemoglobin \<100 g/L

Primary outcomes:
measure: Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels
timeFrame: 1 week prior to surgery (hemoglobin level), and day two of post-op (hemoglobin again).
measure: Trial Feasibility
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: Blood Product Transfusion Rates
timeFrame: Will be measured in the operating room and in the first postoperative week
measure: Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality
timeFrame: Postoperative setting up to 30 days following surgery
measure: Changes in Physiologic Parameters (CVP)
timeFrame: Will be measured in the operating room
measure: Change in Physiologic Parameters (Cardiac Index)
timeFrame: Will be measured in the operating room
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Guillaume Martel, MD, MSc, FRCSC, FACS
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Martel G, Baker L, Wherrett C, Fergusson DA, Saidenberg E, Workneh A, Saeed S, Gadbois K, Jee R, McVicar J, Rao P, Thompson C, Wong P, Abou Khalil J, Bertens KA, Balaa FK. Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility. Br J Surg. 2020 Jun;107(7):812-823. doi: 10.1002/bjs.11463. Epub 2020 Jan 22.
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