Heart DiseaseNCT00744211
Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
A study testing 1mg/kg sitaxsentan sodium and 2mg/kg sitaxsentan sodium in people with Heart Disease, run by VA Office of Research and Development at 1 site in United States.
Trial summary
A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor left ventricular (LV) function (reduced ejection fraction; EF). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Heart Disease
- What is being tested?
- 1mg/kg sitaxsentan sodium and 2mg/kg sitaxsentan sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Apr 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >60 years of age
- Body mass index <40 kg/m2
- Left ventricular ejection fraction less than or equal to 50% documented by a pre-operative echocardiogram
- Patients undergoing coronary artery bypass (CABG), aortic and/or mitral valve replacement or combined CABG and valve procedures requiring CPB.
- If diabetic, be under proper control, (fasting glucose <350 mg/dL or recent hemoglobin A1c [HgbA1c] <9%).
- If hypertensive, be on a stable medical regimen with no significant changes over the past 30 days.
- Female of child bearing potential with a negative pregnancy test, or post-menopausal for at least 2 years
- The patient is an appropriate study candidate as determined by the Investigator on the basis of medical history and physical examination
Who cannot join
- Emergent revascularization
- Previous stroke or thrombo-embolic event in the 3 months prior to study entry
- A previous myocardial infarction within the last 7 days
- Documented coagulopathy
- Hepatic dysfunction as defined by aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 times the upper limit of normal
- Patient is pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5799
About this study
A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor left ventricular (LV) function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF.
Read the detailed description
Patients with a reduced LVEF were prospectively randomized, in a blinded fashion, at the time of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus) or vehicle (saline). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline, at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB.
- Conditions
- Heart Disease
- Being tested
- 1mg/kg sitaxsentan sodium, 2mg/kg sitaxsentan sodium, Vehicle
- Medical subject headings
- Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1mg/kg sitaxsentan sodiumDrug
Also called TBC11251Na
1mg/kg sitaxsentan sodium (intravenous bolus) performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
2mg/kg sitaxsentan sodiumDrug
Also called TBC11251Na
2mg/kg sitaxsentan sodium (intravenous bolus) performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
VehicleOther
Also called Saline
Intravenous bolus performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
| Study group | Role | What they receive |
|---|---|---|
| Vehicle | Placebo comparator | Vehicle Group Receives: Other: Vehicle |
| ET-ARA 1mg/kg | Experimental | ET-ARA 1 mg/kg Receives: Drug: 1mg/kg sitaxsentan sodium |
| ET-ARA 2mg/kg | Experimental | ET-ARA 2 mg/kg Receives: Drug: 2mg/kg sitaxsentan sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary Vascular Resistance
Pulmonary Vascular Resistance (d.s.cm-5)
Measured: Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB)
Secondary outcomes (1)
Plasma Endothelin-1
Plasma Endothelin-1 (fmol/mL)
Measured: Baseline, 0, 6, 12 and 24 hours post-CPB
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionJun 2011
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Heart DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Medical University of South Carolina
- Responsible party
- Sponsor
- Investigators
- Francis Spinale, MD PhD, Principal investigator, Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00744211
- Sponsor's protocol ID
- SURG-001-07F
- Status last verified
- Jul 2026
- First submitted
- 27 Aug 2008
- Last updated
- 13 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Spinale FG, Koval CN, Deschamps AM, Stroud RE, Ikonomidis JS. Dynamic changes in matrix metalloprotienase activity within the human myocardial interstitium during myocardial arrest and reperfusion. Circulation. 2008 Sep 30;118(14 Suppl):S16-23. doi: 10.1161/CIRCULATIONAHA.108.786640.
PubMed 18824748Ford RL, Mains IM, Hilton EJ, Reeves ST, Stroud RE, Crawford FA Jr, Ikonomidis JS, Spinale FG. Endothelin-A receptor inhibition after cardiopulmonary bypass: cytokines and receptor activation. Ann Thorac Surg. 2008 Nov;86(5):1576-83. doi: 10.1016/j.athoracsur.2008.06.076.
PubMed 19049753Toole JM, Ikonomidis JS, Szeto WY, Zellner JL, Mulcahy J, Deardorff RL, Spinale FG. Selective endothelin-1 receptor type A inhibition in subjects undergoing cardiac surgery with preexisting left ventricular dysfunction: Influence on early postoperative hemodynamics. J Thorac Cardiovasc Surg. 2010 Mar;139(3):646-54. doi: 10.1016/j.jtcvs.2009.11.046. Epub 2010 Jan 13.
PubMed 20074751
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
- ClinicalTrials.gov ID
- NCT00744211
- Acronym / sponsor ID
- SURG-001-07F
- Conditions
- Heart Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Medical University of South Carolina
- Study start
- Jul 2008 (actual)
- Primary completion
- Jun 2011 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 29 Aug 2008 (estimated)
- Results
- Posted 9 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor left ventricular (LV) function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF.
Detailed description
Patients with a reduced LVEF were prospectively randomized, in a blinded fashion, at the time of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus) or vehicle (saline). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline, at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vehicle | Placebo comparator | Other: VehicleVehicle Group |
| ET-ARA 1mg/kg | Experimental | Drug: 1mg/kg sitaxsentan sodiumET-ARA 1 mg/kg |
| ET-ARA 2mg/kg | Experimental | Drug: 2mg/kg sitaxsentan sodiumET-ARA 2 mg/kg |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- >60 years of age
- Body mass index <40 kg/m2
- Left ventricular ejection fraction less than or equal to 50% documented by a pre-operative echocardiogram
- Patients undergoing coronary artery bypass (CABG), aortic and/or mitral valve replacement or combined CABG and valve procedures requiring CPB.
- If diabetic, be under proper control, (fasting glucose <350 mg/dL or recent hemoglobin A1c [HgbA1c] <9%).
Key exclusion criteria (6 listed)
- Emergent revascularization
- Previous stroke or thrombo-embolic event in the 3 months prior to study entry
- A previous myocardial infarction within the last 7 days
- Documented coagulopathy
- Hepatic dysfunction as defined by aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 times the upper limit of normal
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 |
|---|---|---|
| 1mg/kg sitaxsentan sodiumAlso: TBC11251Na1mg/kg sitaxsentan sodium (intravenous bolus) performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass. | Drug | ET-ARA 1mg/kg |
| 2mg/kg sitaxsentan sodiumAlso: TBC11251Na2mg/kg sitaxsentan sodium (intravenous bolus) performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass. | Drug | ET-ARA 2mg/kg |
| VehicleAlso: SalineIntravenous bolus performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass. | Other | Vehicle |
Primary outcome
Pulmonary Vascular Resistance
Time frame: Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB)
Pulmonary Vascular Resistance (d.s.cm-5)
1 secondary outcome
Plasma Endothelin-1
Time frame: Baseline, 0, 6, 12 and 24 hours post-CPB
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18824748Spinale FG, Koval CN, Deschamps AM, Stroud RE, Ikonomidis JS. Dynamic changes in matrix metalloprotienase activity within the human myocardial interstitium during myocardial arrest and reperfusion. Circulation. 2008 Sep 30;118(14 Suppl):S16-23. doi: 10.1161/CIRCULATIONAHA.108.786640.
- Results publication: PubMed 19049753Ford RL, Mains IM, Hilton EJ, Reeves ST, Stroud RE, Crawford FA Jr, Ikonomidis JS, Spinale FG. Endothelin-A receptor inhibition after cardiopulmonary bypass: cytokines and receptor activation. Ann Thorac Surg. 2008 Nov;86(5):1576-83. doi: 10.1016/j.athoracsur.2008.06.076.
- Results publication: PubMed 20074751Toole JM, Ikonomidis JS, Szeto WY, Zellner JL, Mulcahy J, Deardorff RL, Spinale FG. Selective endothelin-1 receptor type A inhibition in subjects undergoing cardiac surgery with preexisting left ventricular dysfunction: Influence on early postoperative hemodynamics. J Thorac Cardiovasc Surg. 2010 Mar;139(3):646-54. doi: 10.1016/j.jtcvs.2009.11.046. Epub 2010 Jan 13.
- Individual participant dataSharing planned: No
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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.
Francis Spinale, MD PhD principal investigator
Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1mg/kg sitaxsentan sodium and 2mg/kg sitaxsentan sodium in people with Heart Disease, run by VA Office of Research and Development 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 8 inclusion and 6 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 13 Aug 2026. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 9 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pulmonary Vascular Resistance (time frame: Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB)). 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 NCT00744211, which also lists 3 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 13 Aug 2026.