Hypovolemic Phlebotomy to Reduce Blood Transfusions in Major Hepatic Resections

NCT03651154 | Active Not Recruiting DMC

• 1 other identifier: 502
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 4

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.

Conditions

Liver Neoplasms; Hepatectomy; Blood Transfusion; Blood Loss, Surgical

Outcome Measures

Primary Outcomes (1)

• Packed Red Blood Cell Transfusion Rates

  Units of packed red blood cells transfused to participants

  30 days post-operation

Secondary Outcomes (5)

• Blood product transfusion rates

  Postoperative setting up to 30 days following surgery

• Intraoperative blood loss

  up to 90 days before surgery; and on post-operative day 2

• Perioperative morbidity and mortality

  Postoperative setting up to 30 days following surgery

• Changes in physiologic parameters (Central Venous Pressure)

  measured during surgery (intraoperatively)

• Changes in physiologic parameters (Pulse Pressure Variation)

  measured during surgery (intraoperatively)

Study Arms (2)

Hypovolemic Phlebotomy

EXPERIMENTAL

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

Control (Standard of Care)

NO INTERVENTION

Standard of care (low CVP surgery). In this arm, standard anesthesia will be maintained.

Interventions

Hypovolemic Phlebotomy PROCEDURE

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

Hypovolemic Phlebotomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (4)

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Centre Hospitalier de l"Université de Sherbrooke

Montreal, Quebec, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Location

Related Publications (10)

• Sima CS, Jarnagin WR, Fong Y, Elkin E, Fischer M, Wuest D, D'Angelica M, DeMatteo RP, Blumgart LH, Gonen M. Predicting the risk of perioperative transfusion for patients undergoing elective hepatectomy. Ann Surg. 2009 Dec;250(6):914-21. doi: 10.1097/sla.0b013e3181b7fad3.

  PMID: 19953711 BACKGROUND

• Alkozai EM, Lisman T, Porte RJ. Bleeding in liver surgery: prevention and treatment. Clin Liver Dis. 2009 Feb;13(1):145-154. doi: 10.1016/j.cld.2008.09.012.

  PMID: 19150318 BACKGROUND

• Hallet J, Tsang M, Cheng ES, Habashi R, Kulyk I, Hanna SS, Coburn NG, Lin Y, Law CH, Karanicolas PJ. The Impact of Perioperative Red Blood Cell Transfusions on Long-Term Outcomes after Hepatectomy for Colorectal Liver Metastases. Ann Surg Oncol. 2015 Nov;22(12):4038-45. doi: 10.1245/s10434-015-4477-4. Epub 2015 Mar 10.

  PMID: 25752895 BACKGROUND

• Bennett S, Baker LK, Martel G, Shorr R, Pawlik TM, Tinmouth A, McIsaac DI, Hebert PC, Karanicolas PJ, McIntyre L, Turgeon AF, Barkun J, Fergusson D. The impact of perioperative red blood cell transfusions in patients undergoing liver resection: a systematic review. HPB (Oxford). 2017 Apr;19(4):321-330. doi: 10.1016/j.hpb.2016.12.008. Epub 2017 Feb 1.

  PMID: 28161216 BACKGROUND

• Massicotte L, Perrault MA, Denault AY, Klinck JR, Beaulieu D, Roy JD, Thibeault L, Roy A, McCormack M, Karakiewicz P. Effects of phlebotomy and phenylephrine infusion on portal venous pressure and systemic hemodynamics during liver transplantation. Transplantation. 2010 Apr 27;89(8):920-7. doi: 10.1097/TP.0b013e3181d7c40c.

  PMID: 20216483 BACKGROUND

• Hashimoto T, Kokudo N, Orii R, Seyama Y, Sano K, Imamura H, Sugawara Y, Hasegawa K, Makuuchi M. Intraoperative blood salvage during liver resection: a randomized controlled trial. Ann Surg. 2007 May;245(5):686-91. doi: 10.1097/01.sla.0000255562.60215.3b.

  PMID: 17457160 BACKGROUND

• Ryckx A, Christiaens C, Clarysse M, Vansteenkiste F, Steelant PJ, Sergeant G, Parmentier I, Pottel H, D'Hondt M. Central Venous Pressure Drop After Hypovolemic Phlebotomy is a Strong Independent Predictor of Intraoperative Blood Loss During Liver Resection. Ann Surg Oncol. 2017 May;24(5):1367-1375. doi: 10.1245/s10434-016-5737-7. Epub 2017 Jan 4.

  PMID: 28054191 BACKGROUND

• Rekman J, Wherrett C, Bennett S, Gostimir M, Saeed S, Lemon K, Mimeault R, Balaa FK, Martel G. Safety and feasibility of phlebotomy with controlled hypovolemia to minimize blood loss in liver resections. Surgery. 2017 Mar;161(3):650-657. doi: 10.1016/j.surg.2016.08.026. Epub 2016 Oct 4.

  PMID: 27712877 BACKGROUND

• Martel G, Carrier FM, Wherrett C, Lenet T, Mallette K, Brousseau K, Monette L, Workneh A, Ruel M, Sabri E, Maddison H, Tokessy M, Wong PBY, Vandenbroucke-Menu F, Massicotte L, Chasse M, Collin Y, Perrault MA, Hamel-Perreault E, Park J, Lim S, Maltais V, Leung P, Gilbert RWD, Segedi M, Khalil JA, Bertens KA, Balaa FK, Ramsay T, Tinmouth A, Fergusson DA. Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial. Lancet Gastroenterol Hepatol. 2025 Feb;10(2):114-124. doi: 10.1016/S2468-1253(24)00307-8. Epub 2024 Dec 9.

  PMID: 39667380 DERIVED

• Martel G, Lenet T, Wherrett C, Carrier FM, Monette L, Workneh A, Brousseau K, Ruel M, Chasse M, Collin Y, Vandenbroucke-Menu F, Hamel-Perreault E, Perreault MA, Park J, Lim S, Maltais V, Leung P, Gilbert RWD, Segedi M, Abou-Khalil J, Bertens KA, Balaa FK, Ramsay T, Fergusson DA. Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial. Trials. 2023 Jan 18;24(1):38. doi: 10.1186/s13063-022-07008-y.

  PMID: 36653812 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Blood Loss, Surgical

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Study Officials

• Guillaume Martel, MD, MSc, FRCSC, FACS

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: August 29, 2018
• Study Start: September 28, 2018
• Primary Completion: April 30, 2023
• Study Completion: January 1, 2026
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Upon request during analysis
• Access Criteria: Upon reasonable request, ethics approval and protocol approval from steering committee

Locations

CA (4)