Cardiac SurgeryPhase 3ANHNCT05049590
Acute Normovolemic Hemodilution in Complex Cardiac Surgery
A Phase 3 study testing Acute normovolemic hemodilution (ANH) in people with Cardiac Surgery and Acute Kidney Injury, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Postoperative bleeding in cardiac surgery is a frequent complication, and cardiac surgery utilizes 15-20% of the national blood supply. Packed red blood cells (pRBCs) are associated with worse short and long term outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery, Acute Kidney Injury, Congenital Heart Disease
- What is being tested?
- Acute normovolemic hemodilution (ANH)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2022to 22 Jun 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Adult patients presenting for elective cardiac surgery
- Surgical procedures to include:
- Redo surgery
- Adult congenital heart disease surgery (ACHD)
- Aortic surgery including aortic surgery requiring deep hypothermic circulatory arrest
Who cannot join
- low risk cardiac surgery
- cardiac surgery not requiring cardiopulmonary bypass
- baseline anemia (Hgb < 13 for men and 12 for women)
- post-dilution Hct < 21-24 (basis for this is increased risk of AKI on CPB with Hct 21-22)
- preop treatment for anemia
- high-risk ischemia lesions (critical left main, multi-vessel disease, active/recent chest pain, unstable angina, presence of a balloon pump, recent history of myocardial infarction (MI) either non-ST elevation MI (NSTEMI) / ST-elevation MI (STEMI), regional wall motion abnormalities on echo)
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- low left ventricular systolic function (LVEF < 35-40%) - decompensated heart failure
- Hypertrophic obstructive cardiomyopathy (HOCM) patients with significant left ventricular outflow tract (LVOT) gradients
- history of recent blood transfusion
- history of recent gastrointestinal (GI) bleed
- patient refusal to participate in the study
- severe aortic stenosis (AS) with reduced LVEF
- pulmonary hypertension
- underlying significant liver disease impairing synthetic function (elevated PT/INR or PTT) at baseline
- clotting disorders, inherited or acquired or iatrogenic coagulopathy (i.e. thrombocytopenia, pancytopenia)
- baseline chronic kidney disease (CKD) stage 3/above or End-stage renal disease (ESRD) +/- hemodialysis
- hemodynamically unstable patients including sepsis/recently treated sepsis
- preoperative extracorporeal membrane oxygenation (ECMO) or high suspicion for postoperative ECMO
- emergent cases
Trial locations and contacts
1 site in 1 country.
United States1 site
Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine
Los Angeles, California, 90095
About this study
Official title: Acute Normovolemic Hemodilution (ANH) in Complex Cardiac Surgery
Postoperative bleeding in cardiac surgery is a frequent complication, and cardiac surgery utilizes 15-20% of the national blood supply. Packed red blood cells (pRBCs) are associated with worse short and long term outcomes. For each unit transfused, there is an additive risk of mortality (death) and cardiac adverse events. Despite current guidelines and numerous approaches to bleeding reduction, >50% of the patients undergoing cardiac surgery receive transfusions. Acute normovolemic hemodilution (ANH), a blood conservation technique that removes whole blood from a patient immediately prior to surgery, could be a valuable method to reduce transfusion in complex cardiac surgery. At the University of California, Los Angeles (UCLA), ANH is routinely utilized in patients who refuse allogenic blood transfusions such as Jehovah's Witnesses. ANH has been shown to be safe with minimal risk to patients. ANH has been studied in simple cardiac surgery, such as coronary artery bypass grafting, however it has not been studied in complex cardiac surgery, such as aortic surgery and adult congenital heart disease. ANH has been demonstrated to reduce pRBC transfusion in lower risk cardiac surgery without any significant complications. Complex heart surgery utilizes more blood products. This study could identify the benefits of ANH in a higher risk surgical group.
Read the detailed description
Adult patients undergoing complex heart surgery will be randomized to 1 of 2 groups using block randomization: the intervention arm receiving acute normovolemic hemodilution (ANH) or the control arm receiving standard of care.
As day of surgery hemoglobin (Hgb)/hematocrit (Hct) is critical to the final determination for study participation, patients will be randomized to control or intervention arms after the first intraoperative arterial blood gas (ABG) is obtained. The Hb/Hct obtained from this ABG is used to determine the postdilutional hematocrit using specific pre-ANH and post-ANH equations. Patients with pre-ANH or post-ANH postdilutional Hct lower than 22-24 will not be eligible for inclusion in the ANH arm of the study.
For the Study Group: Using sterile techniques, ANH is performed by removing 8-10cc/kg of whole blood with a maximum of 700cc, from the patient in the OR prior to incision. Whole blood will be collected and stored at room temperature. Hemodynamics are assessed during whole blood removal to ensure adequate stability. ANH will be discontinued if the patient becomes hemodynamically unstable (i.e. significant hypotension greater than 20% reduction from pre-ANH, unstable arrhythmia, evidence of myocardial ischemia or evidence of worsening myocardial function). After whole blood removal, the patient is hydrated to maintain isovolemia with an equivalent volume of crystalloid and/or colloid given, and the blood is stored in the OR at room temperature. After cardiopulmonary bypass (CPB) is complete, the whole blood is returned to the patient. Whole blood stored at room temperature will be transfused within 8 hours of initial collection. After 8 hours, ANH whole blood will be considered expired and will be transfused back to the patient prior to expiration and not discarded. Laboratory coagulation and ROTEM studies (assess blood clotting) will be resent after the ANH blood is returned to the patient. Transfusion requirement will be continuously reassessed based upon laboratory values and surgical assessment of clinical bleeding.
For the Control Group: Blood conservation will not be performed in the OR. Coagulation labs (i.e. platelet count, fibrinogen level and ROTEM studies) are sent while the patient in on bypass. After separation from bypass, coagulation laboratory studies and clinical bleeding are assessed in collaboration with the surgeon. Based on laboratory values and surgical assessment, allogenic transfusions (donor/recipient not the same person) occur in a targeted fashion (i.e. clinical bleeding with platelet count less than 150 x10E3/uL and a ROTEM results indicative of inadequate clot strength will result in platelet transfusion). Transfusion requirements are continuously reassessed based upon updated laboratory values and surgical assessment of clinical bleeding.
Data will also be collected and recorded from the medical record for both groups.
- Being tested
- Acute normovolemic hemodilution (ANH)
- Keywords
- acute normovolemic hemodilution, complex cardiac surgery, transfusions, acute kidney injury
- Medical subject headings
- Acute Kidney Injury, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute normovolemic hemodilution (ANH)Biological
A blood conservation technique that removes whole blood (~8-10cc/kg) from a patient in the operating room prior to incision.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Experimental | Perform blood conservation in the operating room (OR). Receives: Biological: Acute normovolemic hemodilution (ANH) |
| Control Group | No intervention | Blood conservation will not be performed in the OR. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Packed red blood cells (pRBC)
Total transfusion of pRBC units administered 24 hours post-operatively.
Measured: 24 hours
Packed red blood cells (pRBC)
Total transfusion of pRBC units administered 48 hours post-operatively.
Measured: 48 hours
Packed red blood cells (pRBC)
Total transfusion of pRBC units administered 72 hours post-operatively.
Measured: 72 hours
Secondary outcomes (50)
Maximum Intraoperative Vasoactive-Inotropic Score
The maximum intraoperative vasoactive-inotropic score quantifies the amount of cardiovascular support required. The score is calculated based on the highest dose of vasoactive or inotropic drugs used after the conclusion of cardiopulmonary bypass during the intraoperative period. At our institution, the score range is between 0 and 125 with higher scores equating with higher need for support. The drugs included in the calculation include vasopressin, epinephrine, norepinephrine, levosimendan, olprinone, methylene blue, milrinone, phenylephrine, terlipressin, angiotensin II, dobutamine, dopamine and enoximone.
Measured: Conclusion of intraoperative procedure
Maximum 24 Hour Vasoactive-Inotropic Score
The maximum 24 hour vasoactive-inotropic score quantifies the amount of cardiovascular support required over the first 24 hours post-operatively. The score is calculated based on the highest doses of vasoactive and inotropic drugs used during the first 24 hour period postoperatively. At our institution, the score range is between 0 and 125 with higher scores equating with higher need for support. The drugs included in the calculation include vasopressin, epinephrine, norepinephrine, levosimendan, olprinone, methylene blue, milrinone, phenylephrine, terlipressin, angiotensin II, dobutamine, dopamine and enoximone.
Measured: 24 hours
Maximum 48 Hour Vasoactive-Inotropic Score
The maximum 48 hour vasoactive-inotropic score quantifies the amount of cardiovascular support required over the first 48 hours post-operatively. The score is calculated based on the highest doses of vasoactive and inotropic drugs used during the first 48 hour period postoperatively. At our institution, the score range is between 0 and 125 with higher scores equating with higher need for support. The drugs included in the calculation include vasopressin, epinephrine, norepinephrine, levosimendan, olprinone, methylene blue, milrinone, phenylephrine, terlipressin, angiotensin II, dobutamine, dopamine and enoximone.
Measured: 48 hours
Maximum 72 Hour Vasoactive-Inotropic Score
The maximum 72 hour vasoactive-inotropic score quantifies the amount of cardiovascular support required over the first 72 hours post-operatively. The score is calculated based on the highest doses of vasoactive and inotropic drugs used during the first 72 hour period postoperatively. At our institution, the score range is between 0 and 125 with higher scores equating with higher need for support. The drugs included in the calculation include vasopressin, epinephrine, norepinephrine, levosimendan, olprinone, methylene blue, milrinone, phenylephrine, terlipressin, angiotensin II, dobutamine, dopamine and enoximone.
Measured: 72 hours
Acute Kidney Injury (AKI)
Incidence of AKI based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease)/KDIGO (Kidney Disease Improving Global Outcomes) criteria within first 72 hours post-op.
Measured: 72 hours
24 Hour Chest Tube Output
Chest tubes are placed by surgeons at the conclusion of the cases and attached to chest drains. The volume of chest tube drainage is recorded by nurses every 8 hours. The total volume of chest tube output collected in the chest drains will be calculated for the first 24 hours postoperatively.
Measured: 24 Hours
48 Hour Chest Tube Output
Chest tubes are placed by surgeons at the conclusion of the cases and attached to chest drains. The volume of chest tube drainage is recorded by nurses every 8 hours. The total volume of chest tube output collected in the chest drains will be calculated for the first 48 hours postoperatively.
Measured: 48 Hours
72 Hour Chest Tube Output
Chest tubes are placed by surgeons at the conclusion of the cases and attached to chest drains. The volume of chest tube drainage is recorded by nurses every 8 hours. The total volume of chest tube output collected in the chest drains will be calculated for the first 72 hours postoperatively.
Measured: 72 Hours
24 Hour Prothrombin time (PT)
The maximum and minimum prothrombin time (units: seconds) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour Prothrombin time (PT)
The maximum and minimum prothrombin time (units: seconds) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour Prothrombin time (PT)
The maximum and minimum prothrombin time (units: seconds) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
24 Hour International Normalized Ratio (INR)
The maximum and minimum international normalized ratio (units: N/A) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour International Normalized Ratio (INR)
The maximum and minimum international normalized ratio (units: N/A) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour International Normalized Ratio (INR)
The maximum and minimum international normalized ratio (units: N/A) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
24 Hour Activated Partial Thromboplastin time (aPTT)
The maximum and minimum activated partial thromboplastin time (units: seconds) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour Activated Partial Thromboplastin time (aPTT)
The maximum and minimum activated partial thromboplastin time (units: seconds) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour Activated Partial Thromboplastin time (aPTT)
The maximum and minimum activated partial thromboplastin time (units: seconds) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
24 Hour Fibrinogen
The maximum and minimum fibrinogen (units: mg/dL) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour Fibrinogen
The maximum and minimum fibrinogen (units: mg/dL) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour Fibrinogen
The maximum and minimum fibrinogen (units: mg/dL) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
24 Hour Platelet Count
The maximum and minimum platelet count (units: 10E3/uL) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour Platelet Count
The maximum and minimum platelet count (units: 10E3/uL) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour Platelet Count
The maximum and minimum platelet count (units: 10E3/uL) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
24 Hour Hemoglobin (Hgb)
The maximum and minimum hemoglobin (units: g/dL) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour Hemoglobin (Hgb)
The maximum and minimum hemoglobin (units: g/dL) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour Hemoglobin (Hgb)
The maximum and minimum hemoglobin (units: g/dL) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
24 Hour Hematocrit (Hct)
The maximum and minimum hematocrit (units: %) that is collected between hours 0 and 24 postoperatively will be reported.
Measured: 24 hours
48 Hour Hematocrit (Hct)
The maximum and minimum hematocrit (units: %) that is collected between hours 24 and 48 postoperatively will be reported.
Measured: 48 hours
72 Hour Hematocrit (Hct)
The maximum and minimum hematocrit (units: %) that is collected between hours 48 and 72 postoperatively will be reported.
Measured: 72 hours
Rotational Thromboelastometry FIBTEM Maximum Clot Firmness (FIBTEM MCF)
While on cardiopulmonary bypass, rotational thromboelastometry, a point of care viscoelastic test of hemostasis in whole blood, is completed which allows for the quantitative assessment of global clot formation, strength and dissolution. The FIBTEM assesses clot formation via the extrinsic pathway in the presence of cytochalasin D with the resulting clot dependent upon only fibrin formation and fibrin polymerization. The FIBTEM maximum clot firmness (units: mm) is the greatest vertical amplitude of the trace and is indicative of the absolute strength of the clot due to fibrin. A low MCF, less than 7mm, is suggestive of decreased fibrinogen level or polymerization.
Measured: During intraoperative period
Rotational Thromboelastometry HEPTEM/EXTEM Maximum Clot Firmness (HEPTEM/EXTEM MCF)
While on cardiopulmonary bypass, rotational thromboelastometry, a point of care viscoelastic test of hemostasis in whole blood, is completed which allows for the quantitative assessment of global clot formation, strength and dissolution. The HEPTEM assesses clot formation via the intrinsic pathway in the presence of heparinase thereby inactivating circulating heparin, which is appropriate during cardiopulmonary bypass when the patient is systematically heparinized. The EXTEM assesses clot formation via the extrinsic pathway. The HEPTEM/EXTEM maximum clot firmness (units: mm) is the greatest vertical amplitude of the trace and is indicative of the absolute strength of the clot due to fibrinogen and platelets. A low MCF, less than 50mm, is suggestive of decreased platelet number/function or decreased fibrinogen level or polymerization.
Measured: During intraoperative period
Rotational Thromboelastometry EXTEM Clotting Time (EXTEM CT)
While on cardiopulmonary bypass, rotational thromboelastometry, a point of care viscoelastic test of hemostasis in whole blood, is completed which allows for the quantitative assessment of global clot formation, strength and dissolution. The EXTEM assesses clot formation via the extrinsic pathway. The EXTEM clotting time (units: seconds) is the time from start of the measurement until initiation of clotting and is indicative of coagulation factor quantity and function. A high CT, greater than 80 seconds, is suggestive of inadequate clotting factors.
Measured: During intraoperative period
Rotational Thromboelastometry EXTEM Clotting Time (EXTEM A20)
While on cardiopulmonary bypass, rotational thromboelastometry, a point of care viscoelastic test of hemostasis in whole blood, is completed which allows for the quantitative assessment of global clot formation, strength and dissolution. The EXTEM assesses clot formation via the extrinsic pathway. The EXTEM clotting time (units: seconds) is the time from start of the measurement until initiation of clotting and is indicative of coagulation factor quantity and function. A high CT, greater than 80 seconds, is suggestive of inadequate clotting factors.
Measured: During intraoperative period
Rotational Thromboelastometry HEPTEM Clotting Time (HEPTEM CT)
While on cardiopulmonary bypass, rotational thromboelastometry, a point of care viscoelastic test of hemostasis in whole blood, is completed which allows for the quantitative assessment of global clot formation, strength and dissolution. The HEPTEM assesses clot formation via the intrinsic pathway in the presence of heparinase thereby inactivating circulating heparin, which is appropriate during cardiopulmonary bypass when the patient is systematically heparinized. The HEPTEM clotting time (units: seconds) is the time from start of the measurement until initiation of clotting and is indicative of coagulation factor quantity and function. A high HEPTEM CT, greater than 200 seconds, is suggestive of inadequate clotting factors.
Measured: During intraoperative period
Post-cardiopulmonary bypass HEPTEM/EXTEM MCF
We will assess the pre- and post-ANH ROTEM to determine for hemostasis quality by analyzing the viscoelastic properties of the patient's blood clot. We will compare the baseline ROTEM to the on-bypass and post-ANH ROTEM.
Measured: In the operating room (OR) during surgery.
Cerebral oximetry using near infrared spectroscopy derived tissue oxygenation as a marker of perfusion
Intraoperatively, cerebral oximetry using near infrared spectroscopy (NIRS)derived tissue oxygenation is used to grossly monitor grossly cerebral perfusion of the left and right cerebral hemispheres. Values are reported on a scale of 0 (lowest) to 100 (highest). A baseline cerebral oximetry is obtained upon application of the monitoring stickers. Throughout the case, the left and right cerebral oximetry values are reported. We will compare the change in cerebral oximetric value from baseline to values at bypass initiation, bypass separation, after ANH administration and at the case conclusion.
Measured: In the OR during surgery.
Change in mixed venous oxygen saturation as a marker of perfusion
Using a continuous oximetry pulmonary artery catheter, intraoperative and postoperative mixed venous oxygen saturations will be recorded. We will compare the baseline mixed venous oxygen saturation obtained after PAC to the mixed venous oxygen saturation at bypass initiation, bypass separation, post-ANH administration, case conclusion, upon ICU arrival and then 24, 48, 72 hours post-op (or until the PAC is discontinued or discharge from the ICU). A subset of patients may not have PAC placed due to the nature of the surgery. We will not trend/monitor mixed venous in those patients.
Measured: 72 hours
Perfusion markers (lactate)
Intra-op and post-op lactate values. We will compare the baseline lactate (from pre-induction/induction ABG) to the lactate at bypass initiation (30 mins after bypass initiation), at bypass separation, post-ANH administration, case conclusion, upon ICU arrival and then 24/48/72 hours post-op or until discharge from the ICU.
Measured: 72 hours
Delirium
Confusion Assessment Method for the ICU (CAM-ICU)
Measured: Two times per day for up 72 hours post-op or until discharge from the ICU, whichever came first
Number of patients with infection/sepsis
ICU nurses complete a postoperative severe sepsis/shock screen based on white cell counts, temperature, hemodynamics (heart rate and blood pressure) and the presence of any known infectious source (i.e. positive urine culture, blood culture, etc). The total number of patients in the treatment and control arms with reported positive severe sepsis/shock screen will be recorded.
Measured: 72 hours post-op or until discharge from the ICU, whichever came first
Mortality
In-hospital mortality
Measured: An average of 5-10 days until discharge from the hospital, whichever came first
Platelets (PLT)
Total transfusion of PLT units administered 24 hours post-operatively.
Measured: 24 hours
Platelets (PLT)
Total transfusion of PLT units administered 48 hours post-operatively.
Measured: 48 hours
Platelets (PLT)
Total transfusion of PLT units administered 72 hours post-operatively.
Measured: 72 hours
Fresh frozen plasma (FFP)
Total transfusion of FFP units administered 24 hours post-operatively.
Measured: 24 hours
Fresh frozen plasma (FFP)
Total transfusion of FFP units administered 48 hours post-operatively.
Measured: 48 hours
Fresh frozen plasma (FFP)
Total transfusion of FFP units administered 72 hours post-operatively.
Measured: 72 hours
Cryoprecipitate (cryo)
Total transfusion of cryo units administered 24 hours post-operatively.
Measured: 24 hours
Cryoprecipitate (cryo)
Total transfusion of cryo units administered 48 hours post-operatively.
Measured: 48 hours
Cryoprecipitate (cryo)
Total transfusion of cryo units administered 72 hours post-operatively.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2021
- Study start28 Feb 2022
- Primary completion22 May 2023
- Study completion22 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lorraine Lubin, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05049590
- Sponsor's protocol ID
- 21-000469
- Acronym
- ANH
- Status last verified
- May 2024
- First submitted
- 22 Jun 2021
- Last updated
- 5 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 27669554Zhou ZF, Jia XP, Sun K, Zhang FJ, Yu LN, Xing T, Yan M. Mild volume acute normovolemic hemodilution is associated with lower intraoperative transfusion and postoperative pulmonary infection in patients undergoing cardiac surgery -- a retrospective, propensity matching study. BMC Anesthesiol. 2017 Jan 26;17(1):13. doi: 10.1186/s12871-017-0305-7.
PubMed 28122491
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Normovolemic Hemodilution (ANH) in Complex Cardiac Surgery
- ClinicalTrials.gov ID
- NCT05049590
- Acronym / sponsor ID
- ANH / 21-000469
- Keywords
- acute normovolemic hemodilution, complex cardiac surgery, transfusions, acute kidney injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 28 Feb 2022 (actual)
- Primary completion
- 22 May 2023 (actual)
- Study completion
- 22 Jun 2023 (actual)
- First posted
- 20 Sep 2021 (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.
Postoperative bleeding in cardiac surgery is a frequent complication, and cardiac surgery utilizes 15-20% of the national blood supply. Packed red blood cells (pRBCs) are associated with worse short and long term outcomes. For each unit transfused, there is an additive risk of mortality (death) and cardiac adverse events. Despite current guidelines and numerous approaches to bleeding reduction, >50% of the patients undergoing cardiac surgery receive transfusions. Acute normovolemic hemodilution (ANH), a blood conservation technique that removes whole blood from a patient immediately prior to surgery, could be a valuable method to reduce transfusion in complex cardiac surgery. At the University of California, Los Angeles (UCLA), ANH is routinely utilized in patients who refuse allogenic blood transfusions such as Jehovah's Witnesses. ANH has been shown to be safe with minimal risk to patients. ANH has been studied in simple cardiac surgery, such as coronary artery bypass grafting, however it has not been studied in complex cardiac surgery, such as aortic surgery and adult congenital heart disease. ANH has been demonstrated to reduce pRBC transfusion in lower risk cardiac surgery without any significant complications. Complex heart surgery utilizes more blood products. This study could identify the benefits of ANH in a higher risk surgical group.
Detailed description
Adult patients undergoing complex heart surgery will be randomized to 1 of 2 groups using block randomization: the intervention arm receiving acute normovolemic hemodilution (ANH) or the control arm receiving standard of care.
As day of surgery hemoglobin (Hgb)/hematocrit (Hct) is critical to the final determination for study participation, patients will be randomized to control or intervention arms after the first intraoperative arterial blood gas (ABG) is obtained. The Hb/Hct obtained from this ABG is used to determine the postdilutional hematocrit using specific pre-ANH and post-ANH equations. Patients with pre-ANH or post-ANH postdilutional Hct lower than 22-24 will not be eligible for inclusion in the ANH arm of the study.
For the Study Group: Using sterile techniques, ANH is performed by removing 8-10cc/kg of whole blood with a maximum of 700cc, from the patient in the OR prior to incision. Whole blood will be collected and stored at room temperature. Hemodynamics are assessed during whole blood removal to ensure adequate stability. ANH will be discontinued if the patient becomes hemodynamically unstable (i.e. significant hypotension greater than 20% reduction from pre-ANH, unstable arrhythmia, evidence of myocardial ischemia or evidence of worsening myocardial function). After whole blood removal, the patient is hydrated to maintain isovolemia with an equivalent volume of crystalloid and/or colloid given, and the blood is stored in the OR at room temperature. After cardiopulmonary bypass (CPB) is complete, the whole blood is returned to the patient. Whole blood stored at room temperature will be transfused within 8 hours of initial collection. After 8 hours, ANH whole blood will be considered expired and will be transfused back to the patient prior to expiration and not discarded. Laboratory coagulation and ROTEM studies (assess blood clotting) will be resent after the ANH blood is returned to the patient. Transfusion requirement will be continuously reassessed based upon laboratory values and surgical assessment of clinical bleeding.
For the Control Group: Blood conservation will not be performed in the OR. Coagulation labs (i.e. platelet count, fibrinogen level and ROTEM studies) are sent while the patient in on bypass. After separation from bypass, coagulation laboratory studies and clinical bleeding are assessed in collaboration with the surgeon. Based on laboratory values and surgical assessment, allogenic transfusions (donor/recipient not the same person) occur in a targeted fashion (i.e. clinical bleeding with platelet count less than 150 x10E3/uL and a ROTEM results indicative of inadequate clot strength will result in platelet transfusion). Transfusion requirements are continuously reassessed based upon updated laboratory values and surgical assessment of clinical bleeding.
Data will also be collected and recorded from the medical record for both groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Experimental | Biological: Acute normovolemic hemodilution (ANH)Perform blood conservation in the operating room (OR). |
| Control Group | No intervention | –Blood conservation will not be performed in the OR. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients presenting for elective cardiac surgery
- Surgical procedures to include:
Key exclusion criteria (19 listed)
- low risk cardiac surgery
- cardiac surgery not requiring cardiopulmonary bypass
- baseline anemia (Hgb < 13 for men and 12 for women)
- post-dilution Hct < 21-24 (basis for this is increased risk of AKI on CPB with Hct 21-22)
- preop treatment for anemia
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 hemodilution (ANH)A blood conservation technique that removes whole blood (~8-10cc/kg) from a patient in the operating room prior to incision. | Biological | Intervention Group |
Primary outcome
Packed red blood cells (pRBC)
Time frame: 24 hours
Total transfusion of pRBC units administered 24 hours post-operatively.
Packed red blood cells (pRBC)
Time frame: 48 hours
Total transfusion of pRBC units administered 48 hours post-operatively.
Packed red blood cells (pRBC)
Time frame: 72 hours
Total transfusion of pRBC units administered 72 hours post-operatively.
50 secondary outcomes
Maximum Intraoperative Vasoactive-Inotropic Score
Time frame: Conclusion of intraoperative procedure
Maximum 24 Hour Vasoactive-Inotropic Score
Time frame: 24 hours
Maximum 48 Hour Vasoactive-Inotropic Score
Time frame: 48 hours
Maximum 72 Hour Vasoactive-Inotropic Score
Time frame: 72 hours
Acute Kidney Injury (AKI)
Time frame: 72 hours
24 Hour Chest Tube Output
Time frame: 24 Hours
48 Hour Chest Tube Output
Time frame: 48 Hours
72 Hour Chest Tube Output
Time frame: 72 Hours
24 Hour Prothrombin time (PT)
Time frame: 24 hours
48 Hour Prothrombin time (PT)
Time frame: 48 hours
72 Hour Prothrombin time (PT)
Time frame: 72 hours
24 Hour International Normalized Ratio (INR)
Time frame: 24 hours
48 Hour International Normalized Ratio (INR)
Time frame: 48 hours
72 Hour International Normalized Ratio (INR)
Time frame: 72 hours
24 Hour Activated Partial Thromboplastin time (aPTT)
Time frame: 24 hours
48 Hour Activated Partial Thromboplastin time (aPTT)
Time frame: 48 hours
72 Hour Activated Partial Thromboplastin time (aPTT)
Time frame: 72 hours
24 Hour Fibrinogen
Time frame: 24 hours
48 Hour Fibrinogen
Time frame: 48 hours
72 Hour Fibrinogen
Time frame: 72 hours
24 Hour Platelet Count
Time frame: 24 hours
48 Hour Platelet Count
Time frame: 48 hours
72 Hour Platelet Count
Time frame: 72 hours
24 Hour Hemoglobin (Hgb)
Time frame: 24 hours
48 Hour Hemoglobin (Hgb)
Time frame: 48 hours
72 Hour Hemoglobin (Hgb)
Time frame: 72 hours
24 Hour Hematocrit (Hct)
Time frame: 24 hours
48 Hour Hematocrit (Hct)
Time frame: 48 hours
72 Hour Hematocrit (Hct)
Time frame: 72 hours
Rotational Thromboelastometry FIBTEM Maximum Clot Firmness (FIBTEM MCF)
Time frame: During intraoperative period
Rotational Thromboelastometry HEPTEM/EXTEM Maximum Clot Firmness (HEPTEM/EXTEM MCF)
Time frame: During intraoperative period
Rotational Thromboelastometry EXTEM Clotting Time (EXTEM CT)
Time frame: During intraoperative period
Rotational Thromboelastometry EXTEM Clotting Time (EXTEM A20)
Time frame: During intraoperative period
Rotational Thromboelastometry HEPTEM Clotting Time (HEPTEM CT)
Time frame: During intraoperative period
Post-cardiopulmonary bypass HEPTEM/EXTEM MCF
Time frame: In the operating room (OR) during surgery.
Cerebral oximetry using near infrared spectroscopy derived tissue oxygenation as a marker of perfusion
Time frame: In the OR during surgery.
Change in mixed venous oxygen saturation as a marker of perfusion
Time frame: 72 hours
Perfusion markers (lactate)
Time frame: 72 hours
Delirium
Time frame: Two times per day for up 72 hours post-op or until discharge from the ICU, whichever came first
Number of patients with infection/sepsis
Time frame: 72 hours post-op or until discharge from the ICU, whichever came first
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- 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.
- Background: PubMed 28122491Zhou ZF, Jia XP, Sun K, Zhang FJ, Yu LN, Xing T, Yan M. Mild volume acute normovolemic hemodilution is associated with lower intraoperative transfusion and postoperative pulmonary infection in patients undergoing cardiac surgery -- a retrospective, propensity matching study. BMC Anesthesiol. 2017 Jan 26;17(1):13. doi: 10.1186/s12871-017-0305-7.
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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.
Lorraine Lubin, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acute normovolemic hemodilution (ANH) in people with Cardiac Surgery and Acute Kidney Injury, run by University of California, Los Angeles at 1 site in United States.
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 5 inclusion and 19 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: finished, as of the sponsor's last update on 5 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Packed red blood cells (pRBC) (time frame: 24 hours). The study lists 3 primary outcomes in all. 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 NCT05049590, which also lists 2 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 5 Jun 2024.