Acute Normovolemic Hemodilution in High Risk Cardiac Surgery Patients.

NCT03913481 | Active Not Recruiting

• 1 other identifier: ANH/35/OSR
• Study Type: interventional
• Target: 2,000
• Locations: 11 countries
• Sites: 32

Brief Summary

Transfusions are one of the most overused treatments in modern medicine, and saving blood is one important issue all around the world. Cardiac surgery makes up a large percentage of the overall blood components consumption in surgery. Acute normovolemic hemo-dilution (ANH) is a well-known strategy which has been used for years without the support of high quality evidence based medicine to improve post-cardiopulmonary bypass coagulation and reduce red blood cells (RBC) transfusion. We designed a multicenter randomized controlled trial to investigate the effect of ANH in reducing the number of cardiac surgery patients receiving RBC transfusions during hospital stay. We will randomize 2000 patients to have sufficient power to demonstrate a 20% relative and 7% absolute risk reduction in the number of patients' RBC transfusion. If the results of the study will confirm our hypothesis, this will have a great impact on blood management in cardiac operating room.

Conditions

C.Surgical Procedure; Cardiac

Keywords

tissue; organ and systemic injury responses to surgery; trauma; burn; sepsis; hemorrhage; ischemia- reperfusion; resuscitation; including integrating pathways and signals; cardiac surgery; transfusion

Outcome Measures

Primary Outcomes (1)

• RBCs transfusion

  The number of patients receiving RBCs transfusion after elective cardiac surgery.

  hospital discharge, an average of 10 days

Secondary Outcomes (4)

• Mortality

  30 days

• Bleeding complications

  hospital discharge, an average of 10 days

• Ischemic complications

  hospital discharge,an average of 10 days

• AKI

  hospital discharge, an average of 10 days

Study Arms (2)

ANH

EXPERIMENTAL

Best available treatments plus ANH, performed withdrawing a volume of blood before the CPB. The volume will be personalized for every patient, but it'll be at least 650ml.

Procedure: Acute normovolemic hemodilution

Standard care

OTHER

No ANH

Procedure: Standard care

Interventions

Acute normovolemic hemodilution PROCEDURE

In the ANH arm, after induction of general anesthesia, a total blood volume of at least 650 ml of blood will be drawn from a central line. The amount of volume drawn can be replaced with Ringer lactate or a similar crystalloid fluid up to a 3:1 ratio.

ANH

Standard care PROCEDURE

Best available treatment without ANH

Standard care

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Any cardiac surgical intervention on CPB
• Elective surgery

You may not qualify if:

• Medical decision (e.g.: planned pre-CPB ANH considered undeniable for ethical reasons or not applicable for safety issues)
• Unstable Coronary Artery Disease: Recent (\< 6 weeks) myocardial infarction, unstable angina, severe (\> 70%) left main coronary artery stenosis
• Critical preoperative state (ventricular tachycardia or ventricular fibrillation or aborted sudden death, preoperative cardiac massage, preoperative ventilation before anesthetic room, hemodynamic instability, preoperative inotropes or IABP, preoperative severe acute renal failure (anuria or oliguria \<10ml/hr.)
• Emergency surgery
• Pregnancy
• Unfeasibility to withdraw ≥ 650 ml without inducing hemodynamic instability
• Unfeasibility to withdraw ≥ 650 ml without inducing pre-CPB anemia (Htc \<30%)
• Unfeasibility to withdraw ≥ 650 ml without inducing low Htc during CPB (Htc \<24%)

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (32)

OUHSC - University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Mohammed Bin Khalifa Specialist Cardiac Center

Awali, Bahrain, Bahrain

Location

Dante Pazzanese Institute od Cardiology

São Paulo, 04012-909, Brazil

Location

Instituto do Coração - Hospital das Clínicas, Faculdade de Medicina - Universidade de São Paulo

São Paulo, 05403-000, Brazil

Location

Xijing Hospital

Xi'an, 710032, China

Location

Maria Cecilia Hospital

Cotignola, Ravenna, Italy

Location

Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"

Catania, 95123, Italy

Location

Città di Lecce Hospital - GVM Care & Research

Lecce, 73100, Italy

Location

IRCCS Policlinico San Donato

Milan, 20097, Italy

Location

IRCCS Cardiologico Monzino

Milan, 20138, Italy

Location

Ospedale San Raffaele di Milano, Italy

Milan, 20132, Italy

Location

Azienda Ospedaliera Padova

Padua, 35129, Italy

Location

AOU Pisana

Pisa, 56126, Italy

Location

Ospedale San Carlo

Potenza, 85100, Italy

Location

Policlinico Tor Vergata

Rome, 00133, Italy

Location

Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, 00189, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

San Giovanni di Dio e Ruggi d'Aragona

Salerno, 84131, Italy

Location

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Azienda Ospedaliera Ordine Mauriziano di Torino

Torino, 10128, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine

Udine, 33100, Italy

Location

Astrakhan Centre For Cardiac Surgery

Astrakhan, 414011, Russia

Location

Moscow Clinical Scientific Center named after Loginov

Moscow, 111123, Russia

Location

Vishnevsky National Medical Research Center of Surgery

Moscow, 117997, Russia

Location

E. Meshalkin National Medical Research Center

Novosibirsk, Russia

Location

Saint-Petersburg State University Hospital

Saint Petersburg, 190103, Russia

Location

King Abdullah Medical City

Mecca, 24246, Saudi Arabia

Location

Institute of Cardiovascular Diseases "Dedinje"

Belgrade, 11040, Serbia

Location

National University Hospital

Singapore, 119074, Singapore

Location

Chiang Mai University Hospital

Chiang Mai, 50200, Thailand

Location

Kosuyolu High Specialization Education and Research Hospital

Istanbul, 34903, Turkey (Türkiye)

Location

Related Publications (3)

• Monaco F, Guarracino F, Vendramin I, Lei C, Zhang H, Lomivorotov V, Osinsky R, Efremov S, Gurcu ME, Mazzeffi M, Pasyuga V, Kotani Y, Biondi-Zoccai G, D'Ascenzo F, Romagnoli E, Nigro Neto C, Do Nascimento VTNDS, Ti LK, Lorsomradee S, Farag A, Bukamal N, Brizzi G, Lobreglio R, Belletti A, Arangino C, Paternoster G, Bonizzoni MA, Tucciariello MT, Kroeller D, Di Prima AL, Mantovani LF, Ajello V, Gerli C, Porta S, Ferrod F, Giardina G, Santonocito C, Ranucci M, Lembo R, Pisano A, Morselli F, Nakhnoukh C, Oriani A, Pieri M, Scandroglio AM, Kirali K, Likhvantsev V, Longhini F, Yavorovskiy A, Bellomo R, Landoni G, Zangrillo A. Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial. Contemp Clin Trials. 2024 Aug;143:107605. doi: 10.1016/j.cct.2024.107605. Epub 2024 Jun 10.

  PMID: 38866095 BACKGROUND

• Barile L, Fominskiy E, Di Tomasso N, Alpizar Castro LE, Landoni G, De Luca M, Bignami E, Sala A, Zangrillo A, Monaco F. Acute Normovolemic Hemodilution Reduces Allogeneic Red Blood Cell Transfusion in Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Trials. Anesth Analg. 2017 Mar;124(3):743-752. doi: 10.1213/ANE.0000000000001609.

  PMID: 27669554 BACKGROUND

• Monaco F, Lei C, Bonizzoni MA, Efremov S, Morselli F, Guarracino F, Giardina G, Arangino C, Pontillo D, Vitiello M, Belletti A, Ajello V, Licheri M, Nigro Neto C, Barucco G, Bukamal NA, Faustini C, Mantovani LF, Oriani A, Santonocito C, Mucchetti M, Federici F, Gerli C, Porta S, Scandroglio AM, Zhang H, Pieri M, Osinsky R, Lazzari S, Leonova E, Calabro MG, Amitrano D, Turi S, Prati P, Fresilli S, D'Amico F, D'Andria Ursoleo J, Labanca R, Marmiere M, Pruna A, Scquizzato T, Kirali K, Monti G, Carmona MJC, Tanaka K, Likhvantsev V, Ti LK, Bove T, Paternoster G, Singh K, Gurcu ME, Lomivorotov V, Landoni G, Bellomo R, Zangrillo A; ANH Study Group. A Randomized Trial of Acute Normovolemic Hemodilution in Cardiac Surgery. N Engl J Med. 2025 Jul 31;393(5):450-460. doi: 10.1056/NEJMoa2504948. Epub 2025 Jun 12.

  PMID: 40503713 DERIVED

MeSH Terms

Conditions

Wounds and Injuries; Burns; Sepsis; Hemorrhage

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Alberto Zangrillo, Prof

  Vita-Salute University of Milano

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associate Professor

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 12, 2019
• Study Start: April 15, 2019
• Primary Completion: January 19, 2025
• Study Completion: December 1, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

TH (1); BR (2); SG (1); RU (5); CN (1); TU (1); IT (16); SA (1); BA (1); SE (1); US (2)