Abdominal Aortic Aneurysm UncomplicatedPhase 1NCT01681251
Goal Directed Therapy for Patients Undergoing Major Vascular Surgery
A Phase 1 study testing Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13% and Fluid titrated at the discretion of the attending anesthesiologist in people with Abdominal Aortic Aneurysm Uncomplicated, run by University of Manitoba at 1 site in Canada.
Trial summary
The management and delivery of intravenous fluids during surgical operations is one of the important duties for anesthesiologists. The goal of this study was to determine if goal directed fluid therapy, titrated using the FloTrac monitor's measurement of stroke volume variation results in a decrease in the length of… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Abdominal Aortic Aneurysm Uncomplicated
- What is being tested?
- Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13% and Fluid titrated at the discretion of the attending anesthesiologist
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2010to Oct 2013
- Phase
- Phase 1
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- American Society of Anesthesiologists physical class I-III patients over the age of 18 years
- Presenting for elective open repair of abdominal aortic aneurysms.
Who cannot join
- Weight >120kg
- Known or suspected valvular aortic insufficiency
- Renal Dysfunction (serum creatinine >150 μmol/l)
- Pre-existing bowel dysfunction
- Active congestive heart failure
Trial locations and contacts
1 site in 1 country.
About this study
The management and delivery of intravenous fluids during surgical operations is one of the important duties for anesthesiologists.
The goal of this study was to determine if goal directed fluid therapy, titrated using the FloTrac monitor's measurement of stroke volume variation results in a decrease in the length of stay of patients undergoing open abdominal aneurysm repair.
Read the detailed description
The management and delivery of intravenous fluids during surgical operations is one of the important duties for anesthesiologists. There is a growing body of evidence that fluid overload in surgical patients is associated with decreased wound healing, slower return of gut function, anastomotic breakdown, pulmonary edema and post-operative visual changes.
In the United States, abdominal aortic aneurysms are diagnosed in 190,000 people per year, and over 50,000 of those have the aneurysm repaired5. Recent advances in endovascular techniques have allowed many of these patients to forego an open repair. However, because of technical difficulties, many patients still require an open repair.
The most common cause of morbidity in these patients is related to post-operative gastrointestinal tract dysfunction. This usually involves an adynamic ileus that the patients develop on the fourth post-operative day. This delays their tolerance of enteral foods and lengthens their hospital stay and hospital costs. It also has the potential of causing more morbidity in that patients may require total parenteral nutrition while awaiting return of bowel function.
There are several causes of this gastrointestinal morbidity including direct mechanical trauma to the bowel during surgery and activation of the inflammatory cascade. These factors are unfortunately not modifiable by the team caring for the patient. One factor that is modifiable is the amount and type of intravenous fluids administered to the patient.
Typically, anesthesiologists decide on the amount of fluid to administer to patients based on parameters such as heart rate, blood pressure and urine output. These are unfortunately unreliable in determining a patient's volume status, as these parameters can be within the normal range, and a patient might still have inadequate perfusion to their vital organs. Further, clinician's reliance on blood pressure as a target for fluid administration ignores the fact that organs require blood flow as well as pressure to function optimally. Until recently, the only way to measure blood flow was with the insertion of a pulmonary artery catheter. Based on several studies showing a lack of benefit of this invasive procedure, it has fallen out of favor in the non-cardiac arena. Newer monitors of cardiac output that can be attached to a patients arterial catheter (commonly placed for major surgical procedures) offer an alternative method for clinicians to measure cardiac output.
One of these monitors, the FloTrac system (Edwards Life Sciences, Irvine CA), utilizes the arterial pulse contour to calculate cardiac output (CO) and the stroke volume variation (SVV) as a monitor of volume status. In patients who are mechanically ventilated there is a phasic variation in CO and stroke volume based on the ventilatory cycle. Large changes in stroke volume during the ventilatory cycle may indicate hypovolemia in patients. The administration of intravenous fluid to these patients results in a decrease in the SVV. Thus, the SVV can be use a volume monitor and used to titrate intravenous therapy. There have been several trials (mostly in colonic resection surgery) that have looked at such goal directed therapy with this and similar devices and have found a decrease in patient morbidity and length of stay.
All of these studies have in common the use of a minimally invasive CO monitor and a reliance on colloids as the predominant fluid utilized during the case.
The utilization of SVV to determine volume status is a novel approach to fluid management in surgical patients. As stated above, clinicians' historical reliance on pressures (such as as blood pressure and central venous pressure) to estimate intravascular volume status is based on an incomplete understanding on the factors that govern organ blood flow. To this end, the investigators will also assess several parameters during this study in an attempt to ascertain which is the best at predicting fluid responsiveness. Fluid responsiveness is defined as the ability to predict if a given patient will increase their CO to a fluid bolus. To date this has not been looked at in a systematic fashion.
There is also evidence to suggest that such goal directed therapy reduces the degree of inflammation that invariably occurs after operations of this magnitude. It is hypothesized that by resuscitating the endothelium more effectively with intravenous fluids that remain in the intravascular space longer, there is less endothelial damage and thus less inflammation.
- Conditions
- Abdominal Aortic Aneurysm Uncomplicated
- Being tested
- Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13%, Fluid titrated at the discretion of the attending anesthesiologist
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13%Other
Following induction of anesthesia, Voluven boluses of 250ml will be given if SVV increases above 10%. Further Voluven boluses will be given in 250ml aliquots should the SVV increase to greater than 10%. If a total of 55ml/kg of Voluven is given, the fluid will be changed to lactated ringers and no further colloid will be given, as this is the maximum dose recommend by the manufacturer.
Vasoactive agents (type and dose at the discretion of the attending anesthesiologist) may be given to maintain a mean arterial pressure that the clinical team feels adequate to maintain adequate organ perfusion. In the intervention group, however, vasoactive agents will not be given unless fluid administration has resulted in a maximal value of SV.
Fluid titrated at the discretion of the attending anesthesiologistOther
In the control group, the data from the FloTrac monitor will not be available to the anesthesia care provider. Fluid replacement will be at a rate and of a type that is entirely up to the anesthesiologist; the only stipulation being that Voluven is to be used should the provider desire to use a colloid solution.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13% Receives: Other: Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13% |
| Control | Active comparator | Fluid titrated at the discretion of the attending anesthesiologist. Receives: Other: Fluid titrated at the discretion of the attending anesthesiologist |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of Stay
Patients will be assessed for fitness for hospital discharge. This will be used to calculate the length of stay.
Measured: Up to 180 days.
Secondary outcomes (8)
Total Crystalloid Use
Measured: 5 days
Total Colloid Use
Measured: 5 days
Requirement for red blood cell transfusion
Measured: 7 days
Fluid balance
Measured: 7 days
Urine output
Measured: 7 days
Serum creatinine
Measured: 7 days
Postoperative complications
Including: myocardial infarction, sepsis, pneumonia, renal failure, bleeding, ICU admission.
Measured: 28 days
Neutrophil gelatinase associated lipocalnin (NGAL) levels
Measured: Pre-op, immediately post op, 6 hours post-op and 24 hours post-op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2012 (estimated)
- Study startAug 2010
- Primary completionJun 2013
- Study completionOct 2013
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 Abdominal Aortic Aneurysm UncomplicatedStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Duane Funk, University of Manitoba
- Investigators
- Duane J Funk, MD, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01681251
- Sponsor's protocol ID
- B2009:135
- Status last verified
- Nov 2013
- First submitted
- 18 May 2011
- Last updated
- 11 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Brinkman R, HayGlass KT, Mutch WA, Funk DJ. Acute Kidney Injury in Patients Undergoing Open Abdominal Aortic Aneurysm Repair: A Pilot Observational Trial. J Cardiothorac Vasc Anesth. 2015 Oct;29(5):1212-9. doi: 10.1053/j.jvca.2015.03.027. Epub 2015 Apr 1.
PubMed 26275521Funk DJ, HayGlass KT, Koulack J, Harding G, Boyd A, Brinkman R. A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair. Crit Care. 2015 Jun 10;19(1):247. doi: 10.1186/s13054-015-0974-x.
PubMed 26062689
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Goal Directed Therapy for Patients Undergoing Major Vascular Surgery
- ClinicalTrials.gov ID
- NCT01681251
- Acronym / sponsor ID
- B2009:135
- Conditions
- Abdominal Aortic Aneurysm Uncomplicated
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 7 Sep 2012 (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.
The management and delivery of intravenous fluids during surgical operations is one of the important duties for anesthesiologists.
The goal of this study was to determine if goal directed fluid therapy, titrated using the FloTrac monitor's measurement of stroke volume variation results in a decrease in the length of stay of patients undergoing open abdominal aneurysm repair.
Detailed description
The management and delivery of intravenous fluids during surgical operations is one of the important duties for anesthesiologists. There is a growing body of evidence that fluid overload in surgical patients is associated with decreased wound healing, slower return of gut function, anastomotic breakdown, pulmonary edema and post-operative visual changes.
In the United States, abdominal aortic aneurysms are diagnosed in 190,000 people per year, and over 50,000 of those have the aneurysm repaired5. Recent advances in endovascular techniques have allowed many of these patients to forego an open repair. However, because of technical difficulties, many patients still require an open repair.
The most common cause of morbidity in these patients is related to post-operative gastrointestinal tract dysfunction. This usually involves an adynamic ileus that the patients develop on the fourth post-operative day. This delays their tolerance of enteral foods and lengthens their hospital stay and hospital costs. It also has the potential of causing more morbidity in that patients may require total parenteral nutrition while awaiting return of bowel function.
There are several causes of this gastrointestinal morbidity including direct mechanical trauma to the bowel during surgery and activation of the inflammatory cascade. These factors are unfortunately not modifiable by the team caring for the patient. One factor that is modifiable is the amount and type of intravenous fluids administered to the patient.
Typically, anesthesiologists decide on the amount of fluid to administer to patients based on parameters such as heart rate, blood pressure and urine output. These are unfortunately unreliable in determining a patient's volume status, as these parameters can be within the normal range, and a patient might still have inadequate perfusion to their vital organs. Further, clinician's reliance on blood pressure as a target for fluid administration ignores the fact that organs require blood flow as well as pressure to function optimally. Until recently, the only way to measure blood flow was with the insertion of a pulmonary artery catheter. Based on several studies showing a lack of benefit of this invasive procedure, it has fallen out of favor in the non-cardiac arena. Newer monitors of cardiac output that can be attached to a patients arterial catheter (commonly placed for major surgical procedures) offer an alternative method for clinicians to measure cardiac output.
One of these monitors, the FloTrac system (Edwards Life Sciences, Irvine CA), utilizes the arterial pulse contour to calculate cardiac output (CO) and the stroke volume variation (SVV) as a monitor of volume status. In patients who are mechanically ventilated there is a phasic variation in CO and stroke volume based on the ventilatory cycle. Large changes in stroke volume during the ventilatory cycle may indicate hypovolemia in patients. The administration of intravenous fluid to these patients results in a decrease in the SVV. Thus, the SVV can be use a volume monitor and used to titrate intravenous therapy. There have been several trials (mostly in colonic resection surgery) that have looked at such goal directed therapy with this and similar devices and have found a decrease in patient morbidity and length of stay.
All of these studies have in common the use of a minimally invasive CO monitor and a reliance on colloids as the predominant fluid utilized during the case.
The utilization of SVV to determine volume status is a novel approach to fluid management in surgical patients. As stated above, clinicians' historical reliance on pressures (such as as blood pressure and central venous pressure) to estimate intravascular volume status is based on an incomplete understanding on the factors that govern organ blood flow. To this end, the investigators will also assess several parameters during this study in an attempt to ascertain which is the best at predicting fluid responsiveness. Fluid responsiveness is defined as the ability to predict if a given patient will increase their CO to a fluid bolus. To date this has not been looked at in a systematic fashion.
There is also evidence to suggest that such goal directed therapy reduces the degree of inflammation that invariably occurs after operations of this magnitude. It is hypothesized that by resuscitating the endothelium more effectively with intravenous fluids that remain in the intravascular space longer, there is less endothelial damage and thus less inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13%Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13% |
| Control | Active comparator | Other: Fluid titrated at the discretion of the attending anesthesiologistFluid titrated at the discretion of the attending anesthesiologist. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- American Society of Anesthesiologists physical class I-III patients over the age of 18 years
- Presenting for elective open repair of abdominal aortic aneurysms.
Key exclusion criteria (5 listed)
- Weight >120kg
- Known or suspected valvular aortic insufficiency
- Renal Dysfunction (serum creatinine >150 μmol/l)
- Pre-existing bowel dysfunction
- Active congestive heart failure
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 |
|---|---|---|
| Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13%Following induction of anesthesia, Voluven boluses of 250ml will be given if SVV increases above 10%. Further Voluven boluses will be given in 250ml aliquots should the SVV increase to greater than 10%. If a total of 55ml/kg of Voluven is given, the fluid will be changed to lactated ringers and no further colloid will be given, as this is the maximum dose recommend by the manufacturer. Vasoactive agents (type and dose at the discretion of the attending anesthesiologist) may be given to maintain a mean arterial pressure that the clinical team feels adequate to maintain adequate organ perfusion. In the intervention group, however, vasoactive agents will not be given unless fluid administration has resulted in a maximal value of SV. | Other | Intervention |
| Fluid titrated at the discretion of the attending anesthesiologistIn the control group, the data from the FloTrac monitor will not be available to the anesthesia care provider. Fluid replacement will be at a rate and of a type that is entirely up to the anesthesiologist; the only stipulation being that Voluven is to be used should the provider desire to use a colloid solution. | Other | Control |
Primary outcome
Length of Stay
Time frame: Up to 180 days.
Patients will be assessed for fitness for hospital discharge. This will be used to calculate the length of stay.
8 secondary outcomes
Total Crystalloid Use
Time frame: 5 days
Total Colloid Use
Time frame: 5 days
Requirement for red blood cell transfusion
Time frame: 7 days
Fluid balance
Time frame: 7 days
Urine output
Time frame: 7 days
Serum creatinine
Time frame: 7 days
Postoperative complications
Time frame: 28 days
Neutrophil gelatinase associated lipocalnin (NGAL) levels
Time frame: Pre-op, immediately post op, 6 hours post-op and 24 hours post-op
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 11 Nov 2013.
- Derived from this study: PubMed 26275521Brinkman R, HayGlass KT, Mutch WA, Funk DJ. Acute Kidney Injury in Patients Undergoing Open Abdominal Aortic Aneurysm Repair: A Pilot Observational Trial. J Cardiothorac Vasc Anesth. 2015 Oct;29(5):1212-9. doi: 10.1053/j.jvca.2015.03.027. Epub 2015 Apr 1.
- Derived from this study: PubMed 26062689Funk DJ, HayGlass KT, Koulack J, Harding G, Boyd A, Brinkman R. A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair. Crit Care. 2015 Jun 10;19(1):247. doi: 10.1186/s13054-015-0974-x.
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.
Duane J Funk, MD principal investigator
University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13% and Fluid titrated at the discretion of the attending anesthesiologist in people with Abdominal Aortic Aneurysm Uncomplicated, run by University of Manitoba at 1 site in Canada.
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 2 inclusion and 5 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 11 Nov 2013. 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 Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Length of Stay (time frame: Up to 180 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 NCT01681251, 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 11 Nov 2013.