C.Surgical Procedure; CardiacANHNCT03913481
Acute Normovolemic Hemodilution in High Risk Cardiac Surgery Patients.
A study testing Acute normovolemic hemodilution in people with C.Surgical Procedure; Cardiac, run by Università Vita-Salute San Raffaele at 32 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- C.Surgical Procedure; Cardiac
- What is being tested?
- Acute normovolemic hemodilution
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 32 sitesin 11 countries
- Study dates
- 15 Apr 2019to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Any cardiac surgical intervention on CPB
- Elective surgery
Who cannot join
- 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%)
Trial locations and contacts
32 sites in 11 countries.
32 sites in 11 countries
Italy16 sites
Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"
Catania, 95123
Maria Cecilia Hospital
Cotignola, Ravenna
Città di Lecce Hospital - GVM Care & Research
Lecce, 73100
IRCCS Policlinico San Donato
Milan, 20097
IRCCS Cardiologico Monzino
Milan, 20138
Ospedale San Raffaele di Milano, Italy
Milan, 20132
Azienda Ospedaliera Padova
Padua, 35129
AOU Pisana
Pisa, 56126
Ospedale San Carlo
Potenza, 85100
Policlinico Tor Vergata
Rome, 00133
Azienda Ospedaliero-Universitaria Sant'Andrea
Rome, 00189
Istituto Clinico Humanitas
Rozzano, 20089
San Giovanni di Dio e Ruggi d'Aragona
Salerno, 84131
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
Torino, 10126
Azienda Ospedaliera Ordine Mauriziano di Torino
Torino, 10128
Azienda Sanitaria Universitaria Integrata di Udine
Udine, 33100
Russia5 sites
Astrakhan Centre For Cardiac Surgery
Astrakhan, 414011
Moscow Clinical Scientific Center named after Loginov
Moscow, 111123
Vishnevsky National Medical Research Center of Surgery
Moscow, 117997
E. Meshalkin National Medical Research Center
Novosibirsk
Saint-Petersburg State University Hospital
Saint Petersburg, 190103
United States2 sites
University of Virginia
Charlottesville, Virginia, 22903
OUHSC - University of Oklahoma
Oklahoma City, Oklahoma, 73104
Brazil2 sites
Dante Pazzanese Institute od Cardiology
São Paulo, 04012-909
Instituto do Coração - Hospital das Clínicas, Faculdade de Medicina - Universidade de São Paulo
São Paulo, 05403-000
Turkey (Türkiye)1 site
Kosuyolu High Specialization Education and Research Hospital
Istanbul, Turkey, 34903
About this study
Official title: Acute Normovolemic Hemodilution in High-risk Cardiac Surgery Patients. A Multicentre Randomized Trial.
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
- Being tested
- Acute normovolemic hemodilution, Standard care
- Keywords
- tissue, organ and systemic injury responses to surgery, trauma, burn, sepsis, hemorrhage, ischemia- reperfusion, resuscitation, including integrating pathways and signals, cardiac surgery, transfusion
- Medical subject headings
- Wounds and Injuries, Burns, Sepsis, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute normovolemic hemodilutionProcedure or surgery
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.
Standard careProcedure or surgery
Best available treatment without ANH
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Acute normovolemic hemodilution |
| Standard care | Other | No ANH Receives: Procedure: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
RBCs transfusion
The number of patients receiving RBCs transfusion after elective cardiac surgery.
Measured: hospital discharge, an average of 10 days
Secondary outcomes (4)
Mortality
30-day mortality
Measured: 30 days
Bleeding complications
- Amount of blood components (RBC, fresh frozen plasma-FFP, platelet -PLT) transfused (units/ml)
- Estimated total blood volume lost (ml) at 12 hours after surgery
- Surgical revision for bleeding
Measured: hospital discharge, an average of 10 days
Ischemic complications
- Myocardial infarction
- Stroke
- Thromboembolic events
Measured: hospital discharge,an average of 10 days
AKI
Developing of acute kidney injury
Measured: hospital discharge, an average of 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2019
- Study start15 Apr 2019
- Primary completion19 Jan 2025
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for C.Surgical Procedure; CardiacStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
- Investigators
- Alberto Zangrillo, Prof, Study chair, Vita-Salute University of Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03913481
- Sponsor's protocol ID
- ANH/35/OSR
- Acronym
- ANH
- Status last verified
- May 2026
- First submitted
- 9 Apr 2019
- Last updated
- 8 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38866095Barile 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.
PubMed 27669554Pruna A, Scandroglio AM, Lei C, Oriani A, Di Fazio A, Pontillo D, Santonocito C, Bonizzoni MA, Comis M, Calabro MG, Kadantseva K, Barucco G, Guarracino F, Giardina G, Ajello V, Di Prima AL, Osinsky R, Oliva FM, Efremov S, Mucchetti M, Vandyck KB, Franco A, Arangino C, Nardelli P, Ranucci M, D'Amora M, Wang L, Zhang H, Lorsomradee S, Hajjar LA, Ti LK, McNeil JS, Pieri M, Bove T, Gurcu ME, Rocco M, Landoni G, Paternoster G, Zangrillo A, Monaco F; ANH Study Group. Safety and Efficacy of Acute Normovolemic Hemodilution in Female Patients: A Secondary Analysis of the ANH Trial. JAMA Surg. 2026 Oct 14. doi: 10.1001/jamasurg.2026.4786. Online ahead of print.
PubMed 42873487Monaco 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.
PubMed 40503713
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Normovolemic Hemodilution in High-risk Cardiac Surgery Patients. A Multicentre Randomized Trial.
- ClinicalTrials.gov ID
- NCT03913481
- Acronym / sponsor ID
- ANH / ANH/35/OSR
- Conditions
- C.Surgical Procedure; Cardiac
- Keywords
- tissue, organ and systemic injury responses to surgery, trauma, burn, sepsis, hemorrhage, ischemia- reperfusion, resuscitation
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 19 Jan 2025 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ANH | Experimental | Procedure: Acute normovolemic hemodilutionBest 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. |
| Standard care | Other | Procedure: Standard careNo ANH |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Signed informed consent
- Any cardiac surgical intervention on CPB
- Elective surgery
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute normovolemic hemodilutionIn 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. | Procedure or surgery | ANH |
| Standard careBest available treatment without ANH | Procedure or surgery | Standard care |
Primary outcome
RBCs transfusion
Time frame: hospital discharge, an average of 10 days
The number of patients receiving RBCs transfusion after elective cardiac surgery.
4 secondary outcomes
Mortality
Time frame: 30 days
Bleeding complications
Time frame: hospital discharge, an average of 10 days
Ischemic complications
Time frame: hospital discharge,an average of 10 days
AKI
Time frame: hospital discharge, an average of 10 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Background: PubMed 38866095Monaco 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.
- Background: PubMed 27669554Barile 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.
- Derived from this study: PubMed 42873487Pruna A, Scandroglio AM, Lei C, Oriani A, Di Fazio A, Pontillo D, Santonocito C, Bonizzoni MA, Comis M, Calabro MG, Kadantseva K, Barucco G, Guarracino F, Giardina G, Ajello V, Di Prima AL, Osinsky R, Oliva FM, Efremov S, Mucchetti M, Vandyck KB, Franco A, Arangino C, Nardelli P, Ranucci M, D'Amora M, Wang L, Zhang H, Lorsomradee S, Hajjar LA, Ti LK, McNeil JS, Pieri M, Bove T, Gurcu ME, Rocco M, Landoni G, Paternoster G, Zangrillo A, Monaco F; ANH Study Group. Safety and Efficacy of Acute Normovolemic Hemodilution in Female Patients: A Secondary Analysis of the ANH Trial. JAMA Surg. 2026 Oct 14. doi: 10.1001/jamasurg.2026.4786. Online ahead of print.
- Derived from this study: PubMed 40503713Monaco 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alberto Zangrillo, Prof study chair
Vita-Salute University of Milano
32 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute normovolemic hemodilution in people with C.Surgical Procedure; Cardiac, run by Università Vita-Salute San Raffaele at 32 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Italy, Russia, United States, Brazil, Bahrain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RBCs transfusion (time frame: hospital discharge, an average of 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03913481, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.