PancreaticoduodenectomyPhase 3NCT00200148
Acute Normovolemic Hemodilution Versus Standard Intraoperative Management in Patients Having Hepatic Resection and Pancreaticoduodenectomy
A Phase 3 study testing Normovolemic Hemodilution (ANH) in people with Pancreaticoduodenectomy and Hepatectomy, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
With a major liver or pancreas operation, there is a chance that one will require a transfusion of blood products (either red blood cells or plasma). This may be necessary during the operation or a few days after surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreaticoduodenectomy, Hepatectomy
- What is being tested?
- Normovolemic Hemodilution (ANH)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 372 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Oct 2011
- 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
- Adults (>18 years).
- Pre-operative hemoglobin concentration >= 11 mg/dl (males); >= 10 mg/dl (females) within 14 days of registration.
- Patients scheduled for resection of 3 or more liver segments for any indication, with or without other planned procedures or patients scheduled for pancreaticoduodenectomy
Who cannot join
- A history of active coronary artery disease. Patients with a history of coronary artery disease will be eligible if they have had a cardiac stress study showing no reversible ischemia and normal left ventricular (LV) function within 30 days of operation.
- A history of cerebrovascular disease.
- A history of congestive heart failure.
- A history of uncontrolled hypertension.
- A history of restrictive or obstructive pulmonary disease.
- A history of renal dysfunction (creatinine [Cr] > 1.8).
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- Abnormal coagulation parameters (International Normalized Ratio [INR] > 1.5 not on Coumadin, or platelet count < 100,000).
- Presence of active infection.
- Evidence of hepatic metabolic disorder (bilirubin > 2 mg/dl, ALT > 75 U/L in the absence of biliary tract obstruction).
- Pre-operative autologous blood donation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
Official title: A Prospective Randomized Trial of Acute Normovolemic Hemodilution Compared to Standard Intraoperative Management in Patients Undergoing Major Hepatic Resection and Pancreaticoduodenectomy
With a major liver or pancreas operation, there is a chance that one will require a transfusion of blood products (either red blood cells or plasma). This may be necessary during the operation or a few days after surgery. The surgeons at Memorial Sloan-Kettering Cancer Center perform a very large number of liver or pancreas resections every year and have pioneered techniques that minimize bleeding during the operation. Even so, liver or pancreas operations such as the one that will be undergone carry a 50% chance of requiring a transfusion. A technique that might lower the need for transfusions is called acute normovolemic hemodilution (ANH). ANH was first introduced over twenty years ago and has been used in many types of operations, including liver or pancreas resection. The studies done on ANH at other hospitals suggest that it may help conserve blood. Researchers at Memorial Sloan-Kettering Cancer Center are conducting a study to determine if ANH is better than the 'standard technique' that is currently used in all patients. The purpose of this study is to find out which of the two techniques is better.
The purpose of the study is to see if ANH lowers the need for the transfusion of blood products during and after liver or pancreas resection.
The second purpose of the study is to see how ANH changes the length of the operation, the length of time one spends in the hospital, and the complication rate after surgery. The researchers will also see if ANH requires any changes in the administration of anesthesia.
Read the detailed description
Despite improvements in peri-operative outcome, major hepatic resection and pancreaticoduodenectomy remains associated with a high risk of major blood loss and perioperative blood transfusion.The risks associated with allogeneic blood transfusions are well-known, including immunosuppression, incompatible transfusion, and transmission of infectious agents. Clearly, efforts to reduce the use of allogeneic blood products are warranted in order to avoid potential transfusion-related complications, reduce hospital cost and avoid periods of critical blood shortage.
ANH is an approach to blood conservation that involves removal of whole blood from a patient immediately prior to an operation that is likely to be associated with significant blood loss. Following blood removal, euvolemia is restored with crystalloid and/or colloid. The harvested blood, which has a greater red cell mass than the blood lost intraoperatively, is re-infused as needed during the procedure or at the completion of the operation. ANH is more attractive than preoperative autologous blood donation for several reasons: it is technically and logistically much simpler, it requires no special equipment and costs less (no storage or administrative costs), it is associated with a lower chance of administration error, it requires no obligate pre-operative delay and is not associated with a waste of autologous units. In addition, because coagulation factors are preserved and later re-infused, ANH may reduce the need for post-operative fresh frozen plasma (FFP). Additionally, ANH may have an impact on low CVP anesthetic management during partial hepatectomy, which is standard at MSKCC and at many other centers.
The present study will help elucidate the efficacy of ANH as a means of reducing the allogeneic transfusion rate in patients undergoing major hepatic resection. If shown to be effective in reducing the use of allogeneic blood products, ANH will not only impact the current practice of hepatic resectional surgery but may also change current practice in other surgical disciplines.
This will be a prospective randomized study. Eligible patients will be consented for the trial prior to the operation.
- Conditions
- Pancreaticoduodenectomy, Hepatectomy
- Being tested
- Normovolemic Hemodilution (ANH), Standard of care
- Keywords
- Pancreaticoduodenectomy, Hepatectomy, Major Hepatic resection, Acute Normovolemic Hemodilution
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normovolemic Hemodilution (ANH)Procedure or surgery
For those patients randomized to ANH, the pre-calculated volume of blood will be withdrawn to a target hemoglobin of 8.0 - 8.5 g/dl (maximum of 3 L) using the formula VL=EBV x (HO-HF)/Hav, as above. The removed blood will be stored in a standard citrate-phosphate-dextrose buffer solution in blood storage bags in the operating room. During removal of blood, colloid and crystalloid solutions will be administered via peripheral intravenous lines in order to maintain euvolemia. For all patients, arterial blood will be sampled every 30 minutes during the resection for assessment of arterial blood gases/pH; Hgb levels will be measured every 30 minutes.For patients randomized to ANH, autologous blood will be re-infused in the reverse order from which it was removed, and allogeneic blood will given only after all autologous blood has been given.
Standard of careProcedure or surgery
An 8.5 French central venous catheter and an arterial line will be placed in all patients. If the patient has a central line already in place, this may be used in place of the 8.5 French internal jugular catheter. Continuous monitoring of heart rate, blood pressure, ECG (II, V5), CVP, end tidal CO2, oxygen saturation, temperature and urine output will be performed for all patients.For all hepatic resections, standard low CVP anesthetic management will be employed.For all patients, arterial blood will be sampled every 30 minutes during the resection for assessment of arterial blood gases/pH; Hgb levels will be measured every 30 minutes.All patients will receive standard postoperative management. Routine laboratory studies, including comprehensive panel, CBC and coagulation profile, will be obtained daily in the post-operative period.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | For patients randomized to ANH Receives: Procedure: Normovolemic Hemodilution (ANH) |
| 2 | Active comparator | standard intraoperative management Receives: Procedure: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if ANH reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection or pancreaticoduodenectomy compared to standard intraoperative management
Measured: All patients will have their blood checked every 30 minutes during surgery
Secondary outcomes (3)
To determine if ANH reduces the requirement for allogeneic FFP transfusions in patients undergoing major hepatic resection or pancreaticoduodenectomy compared to standard intraoperative management
Measured: All patients will have their blood checked every 30 minutes during surgery
To determine the impact of ANH on post-operative complications, length of hospital stay and operating time compared to standard intraoperative management
Measured: Two weeks
To assess the impact of ANH on low central venous pressure (CVP) anesthetic management during partial hepatectomy
Measured: Continuous monitoring during surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startMar 2004
- Primary completionOct 2011
- Study completionOct 2011
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 PancreaticoduodenectomyStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 372 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William R. Jarnagin, M.D., Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00200148
- Sponsor's protocol ID
- 04-004
- Status last verified
- Mar 2015
- First submitted
- 12 Sep 2005
- Last updated
- 6 Mar 2015
- Results posted
- No
Publications
Fischer M, Matsuo K, Gonen M, Grant F, Dematteo RP, D'Angelica MI, Mascarenhas J, Brennan MF, Allen PJ, Blumgart LH, Jarnagin WR. Relationship between intraoperative fluid administration and perioperative outcome after pancreaticoduodenectomy: results of a prospective randomized trial of acute normovolemic hemodilution compared with standard intraoperative management. Ann Surg. 2010 Dec;252(6):952-8. doi: 10.1097/SLA.0b013e3181ff36b1.
PubMed 21107104Jarnagin WR, Gonen M, Maithel SK, Fong Y, D'Angelica MI, Dematteo RP, Grant F, Wuest D, Kundu K, Blumgart LH, Fischer M. A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection. Ann Surg. 2008 Sep;248(3):360-9. doi: 10.1097/SLA.0b013e318184db08.
PubMed 18791356
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Trial of Acute Normovolemic Hemodilution Compared to Standard Intraoperative Management in Patients Undergoing Major Hepatic Resection and Pancreaticoduodenectomy
- ClinicalTrials.gov ID
- NCT00200148
- Acronym / sponsor ID
- 04-004
- Conditions
- Pancreaticoduodenectomy, Hepatectomy
- Keywords
- Pancreaticoduodenectomy, Hepatectomy, Major Hepatic resection, Acute Normovolemic Hemodilution
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 372 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- Mar 2004
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 20 Sep 2005 (estimated)
- 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.
With a major liver or pancreas operation, there is a chance that one will require a transfusion of blood products (either red blood cells or plasma). This may be necessary during the operation or a few days after surgery. The surgeons at Memorial Sloan-Kettering Cancer Center perform a very large number of liver or pancreas resections every year and have pioneered techniques that minimize bleeding during the operation. Even so, liver or pancreas operations such as the one that will be undergone carry a 50% chance of requiring a transfusion. A technique that might lower the need for transfusions is called acute normovolemic hemodilution (ANH). ANH was first introduced over twenty years ago and has been used in many types of operations, including liver or pancreas resection. The studies done on ANH at other hospitals suggest that it may help conserve blood. Researchers at Memorial Sloan-Kettering Cancer Center are conducting a study to determine if ANH is better than the 'standard technique' that is currently used in all patients. The purpose of this study is to find out which of the two techniques is better.
The purpose of the study is to see if ANH lowers the need for the transfusion of blood products during and after liver or pancreas resection.
The second purpose of the study is to see how ANH changes the length of the operation, the length of time one spends in the hospital, and the complication rate after surgery. The researchers will also see if ANH requires any changes in the administration of anesthesia.
Detailed description
Despite improvements in peri-operative outcome, major hepatic resection and pancreaticoduodenectomy remains associated with a high risk of major blood loss and perioperative blood transfusion.The risks associated with allogeneic blood transfusions are well-known, including immunosuppression, incompatible transfusion, and transmission of infectious agents. Clearly, efforts to reduce the use of allogeneic blood products are warranted in order to avoid potential transfusion-related complications, reduce hospital cost and avoid periods of critical blood shortage.
ANH is an approach to blood conservation that involves removal of whole blood from a patient immediately prior to an operation that is likely to be associated with significant blood loss. Following blood removal, euvolemia is restored with crystalloid and/or colloid. The harvested blood, which has a greater red cell mass than the blood lost intraoperatively, is re-infused as needed during the procedure or at the completion of the operation. ANH is more attractive than preoperative autologous blood donation for several reasons: it is technically and logistically much simpler, it requires no special equipment and costs less (no storage or administrative costs), it is associated with a lower chance of administration error, it requires no obligate pre-operative delay and is not associated with a waste of autologous units. In addition, because coagulation factors are preserved and later re-infused, ANH may reduce the need for post-operative fresh frozen plasma (FFP). Additionally, ANH may have an impact on low CVP anesthetic management during partial hepatectomy, which is standard at MSKCC and at many other centers.
The present study will help elucidate the efficacy of ANH as a means of reducing the allogeneic transfusion rate in patients undergoing major hepatic resection. If shown to be effective in reducing the use of allogeneic blood products, ANH will not only impact the current practice of hepatic resectional surgery but may also change current practice in other surgical disciplines.
This will be a prospective randomized study. Eligible patients will be consented for the trial prior to the operation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Normovolemic Hemodilution (ANH)For patients randomized to ANH |
| 2 | Active comparator | Procedure: Standard of carestandard intraoperative management |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults (>18 years).
- Pre-operative hemoglobin concentration >= 11 mg/dl (males); >= 10 mg/dl (females) within 14 days of registration.
- Patients scheduled for resection of 3 or more liver segments for any indication, with or without other planned procedures or patients scheduled for pancreaticoduodenectomy
Key exclusion criteria (10 listed)
- A history of active coronary artery disease. Patients with a history of coronary artery disease will be eligible if they have had a cardiac stress study showing no reversible ischemia and normal left ventricular (LV) function within 30 days of operation.
- A history of cerebrovascular disease.
- A history of congestive heart failure.
- A history of uncontrolled hypertension.
- A history of restrictive or obstructive pulmonary disease.
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 |
|---|---|---|
| Normovolemic Hemodilution (ANH)For those patients randomized to ANH, the pre-calculated volume of blood will be withdrawn to a target hemoglobin of 8.0 - 8.5 g/dl (maximum of 3 L) using the formula VL=EBV x (HO-HF)/Hav, as above. The removed blood will be stored in a standard citrate-phosphate-dextrose buffer solution in blood storage bags in the operating room. During removal of blood, colloid and crystalloid solutions will be administered via peripheral intravenous lines in order to maintain euvolemia. For all patients, arterial blood will be sampled every 30 minutes during the resection for assessment of arterial blood gases/pH; Hgb levels will be measured every 30 minutes.For patients randomized to ANH, autologous blood will be re-infused in the reverse order from which it was removed, and allogeneic blood will given only after all autologous blood has been given. | Procedure or surgery | 1 |
| Standard of careAn 8.5 French central venous catheter and an arterial line will be placed in all patients. If the patient has a central line already in place, this may be used in place of the 8.5 French internal jugular catheter. Continuous monitoring of heart rate, blood pressure, ECG (II, V5), CVP, end tidal CO2, oxygen saturation, temperature and urine output will be performed for all patients.For all hepatic resections, standard low CVP anesthetic management will be employed.For all patients, arterial blood will be sampled every 30 minutes during the resection for assessment of arterial blood gases/pH; Hgb levels will be measured every 30 minutes.All patients will receive standard postoperative management. Routine laboratory studies, including comprehensive panel, CBC and coagulation profile, will be obtained daily in the post-operative period. | Procedure or surgery | 2 |
Primary outcome
To determine if ANH reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection or pancreaticoduodenectomy compared to standard intraoperative management
Time frame: All patients will have their blood checked every 30 minutes during surgery
3 secondary outcomes
To determine if ANH reduces the requirement for allogeneic FFP transfusions in patients undergoing major hepatic resection or pancreaticoduodenectomy compared to standard intraoperative management
Time frame: All patients will have their blood checked every 30 minutes during surgery
To determine the impact of ANH on post-operative complications, length of hospital stay and operating time compared to standard intraoperative management
Time frame: Two weeks
To assess the impact of ANH on low central venous pressure (CVP) anesthetic management during partial hepatectomy
Time frame: Continuous monitoring during surgery
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 6 Mar 2015.
- Derived from this study: PubMed 21107104Fischer M, Matsuo K, Gonen M, Grant F, Dematteo RP, D'Angelica MI, Mascarenhas J, Brennan MF, Allen PJ, Blumgart LH, Jarnagin WR. Relationship between intraoperative fluid administration and perioperative outcome after pancreaticoduodenectomy: results of a prospective randomized trial of acute normovolemic hemodilution compared with standard intraoperative management. Ann Surg. 2010 Dec;252(6):952-8. doi: 10.1097/SLA.0b013e3181ff36b1.
- Derived from this study: PubMed 18791356Jarnagin WR, Gonen M, Maithel SK, Fong Y, D'Angelica MI, Dematteo RP, Grant F, Wuest D, Kundu K, Blumgart LH, Fischer M. A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection. Ann Surg. 2008 Sep;248(3):360-9. doi: 10.1097/SLA.0b013e318184db08.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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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.
William R. Jarnagin, M.D. principal investigator
Memorial Sloan Kettering Cancer Center
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 Normovolemic Hemodilution (ANH) in people with Pancreaticoduodenectomy and Hepatectomy, run by Memorial Sloan Kettering Cancer Center 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 3 inclusion and 10 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 6 Mar 2015. 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?
To determine if ANH reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection or pancreaticoduodenectomy compared to standard intraoperative management (time frame: All patients will have their blood checked every 30 minutes during surgery). 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 NCT00200148, 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 6 Mar 2015.