Endothelial DysfunctionNCT02882074
Endothelial Function After Cardiac Surgery
A study testing Human albumin and Hydroxyethyl starch in people with Endothelial Dysfunction, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The purpose of this study is to evaluate whether patients receiving human albumin for plasma volume replacement during cardiac surgery have improved postoperative endothelial function compared to patients receiving 6% hydroxyethyl starch solutions. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Endothelial Dysfunction
- What is being tested?
- Human albumin and Hydroxyethyl starch
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 20 Feb 2020
- 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 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 40 - 85 years old
- Scheduled for elective aortic valve replacement with or without coronary artery bypass grafting with or without additional minor surgical procedure.
- Written, informed consent for participation in this investigation.
Who cannot join
- Patients with Raynaud's disease or other disease associated with upper extremity vascular insufficiency,
- Inability to perform EndoPAT exam (inability to lie still for 15 min, or significant finger deformity),
- Patients with renal failure with oliguria or anuria not related to hypovolemia.
- Patients receiving dialysis.
- Patients with preoperative renal insufficiency (Creatinine > 1.6 mg/dL)
- Anticipated deep hypothermic circulatory arrest
Show all 15Show fewer
- Known hypersensitivity or allergy to hydroxyethyl starch or the excipients of hydroxyethyl starch
- Clinical conditions with volume overload (e.g., patients in pulmonary edema or congestive heart failure)
- Patients with severe hypernatremia or severe hyperchloremia
- Patients with intracranial bleeding
- Pregnant or breast feeding women
- Critically ill adult patients, including patients with sepsis, due to increased risk of mortality and renal replacement therapy, (e.g. patients who are hospitalized in the intensive care unit prior to surgery)
- Severe liver disease
- Pre-existing coagulation or bleeding disorders
- Any contraindications to proposed interventions.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Plasma Volume Replacement With 5% Human Albumin Reduce Endothelial Injury and Glycocalyceal Disruption Compared With 6% Hydroxyethylstarch (130/0.4) in Patients Having Cardiac Surgery? A Substudy of the SHARP Clinical Trial
The purpose of this study is to evaluate whether patients receiving human albumin for plasma volume replacement during cardiac surgery have improved postoperative endothelial function compared to patients receiving 6% hydroxyethyl starch solutions. The postoperative endothelial function, measured with peripheral arterial tonometry as reactive hyperemia index (RHI) within 2 hours following surgery, will be compared in cardiac surgical patients randomized to receive human albumin or 6% HES solutions for intraoperative volume replacement. Within two hours of arrival to the ICU peripheral arterial tonometry using EndoPAT will be performed. In a subset of 40 consecutive patients the investigators will perform additional EndoPAT measurements to describe the expected changes that occur in endothelial function during the perioperative period (baseline, early postoperative and 24 hours postoperative) using RHI.
This study will also determine whether human albumin 5% reduces plasma biomarkers of endothelial and glycocalyceal damage by measuring plasma concentrations of syndecan 1 and endocan at baseline (before surgery), and 1 and 24 hours following surgery. Blood samples will be taken on the morning of the surgery, within one hour of arrival to the intensive care unit (ICU), and 24 hours after surgery or within 2 hours before discharge from the ICU (three times altogether). These samples will be used to measure the plasma concentrations of two biomarkers that measure endothelial injury.
Read the detailed description
Cardiac surgical patients enrolled in the SHARP study will be randomized to 5% human albumin or 6% HES on entrance to the operating room. Anesthetic and Surgical management will follow protocol established by SHARP study including administration of a blinded study solution which contains 5% human albumin or 6% HES following separation from cardiopulmonary bypass. Blood will collected for measurement of baseline syndecan 1 and endocan following arterial line and urinary catheter placement before surgical incision. At 1 and 24 hrs following surgery completion, blood will be collected for measurement of syndecan 1 and endocan. Within two hours of ICU arrival, assessment of endothelial function will be performed.
In a subset of patients (patients who consent for multiple measurements), assessment of endothelial function will be performed preoperatively (baseline) and 24 hours after surgery.
Vasoactive substances may influence EndoPAT measurement. Thus the investigators will collect data on use of preoperative antihypertensive medications that have direct or indirect effect on arterial smooth muscle relaxation. Use of epinephrine, norepinephrine, vasopressin, milrinone, nitroglycerine, nitroprusside, and sedatives such as propofol, dexmedetomidine and others will be recorded and adjusted for in the analysis. Data on packed red blood cells (PRBC) and blood component transfusion will be collected from Anesthesia Record Keeping System. Indications for PRBC transfusion include hematocrit (HCT) <22% on cardiopulmonary bypass and <24% off cardiopulmonary bypass, and hypovolemia with anemia (HCT<25% with mean arterial blood pressure <60 mmHg or heart rate >100 bpm). Blood component transfusion (platelets, fresh frozen plasma, cryoprecipitate) may be administered as necessary following institutional standard of care. Imbalances in blood product transfusion between study groups will be adjusted for in the analysis.
- Conditions
- Endothelial Dysfunction
- Being tested
- Human albumin, Hydroxyethyl starch
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human albuminDrug
Also called albumin
human albumin 5% during surgery
Hydroxyethyl starchDrug
Also called HES
6% Hydroxyethyl starch 130/0.4 during surgery
| Study group | Role | What they receive |
|---|---|---|
| Human albumin | Other | Human albumin 5% during surgery. Receives: Drug: Human albumin |
| Hydroxyethyl starch | Other | Hydroxyethyl starch 6% (130/0.4) solution during surgery Receives: Drug: Hydroxyethyl starch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reactive Hyperemia Index (RHI)
RHI measures endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT) with the EndoPAT device. It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered a sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. Increasing score indicates the improvement of coronary endothelial function.
Measured: 2 hours after surgery
Secondary outcomes (2)
Plasma Concentrations of Syndecan
Blood samples will be obtained at specified times
Measured: 1 hour after surgery, 24 hours after surgery
Plasma Concentrations of Endocan
Blood samples will be obtained at specified times
Measured: 1 hour after surgery, 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2016 (estimated)
- Study startJun 2016
- Primary completion20 Feb 2020
- Study completion20 Feb 2020
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.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Sessler, M.D., Study chair, Department Chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02882074
- Sponsor's protocol ID
- 16-342
- Status last verified
- Jan 2024
- First submitted
- 17 Aug 2016
- Last updated
- 1 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Plasma Volume Replacement With 5% Human Albumin Reduce Endothelial Injury and Glycocalyceal Disruption Compared With 6% Hydroxyethylstarch (130/0.4) in Patients Having Cardiac Surgery? A Substudy of the SHARP Clinical Trial
- ClinicalTrials.gov ID
- NCT02882074
- Acronym / sponsor ID
- 16-342
- Conditions
- Endothelial Dysfunction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 20 Feb 2020 (actual)
- First posted
- 29 Aug 2016 (estimated)
- Results
- Posted 1 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate whether patients receiving human albumin for plasma volume replacement during cardiac surgery have improved postoperative endothelial function compared to patients receiving 6% hydroxyethyl starch solutions. The postoperative endothelial function, measured with peripheral arterial tonometry as reactive hyperemia index (RHI) within 2 hours following surgery, will be compared in cardiac surgical patients randomized to receive human albumin or 6% HES solutions for intraoperative volume replacement. Within two hours of arrival to the ICU peripheral arterial tonometry using EndoPAT will be performed. In a subset of 40 consecutive patients the investigators will perform additional EndoPAT measurements to describe the expected changes that occur in endothelial function during the perioperative period (baseline, early postoperative and 24 hours postoperative) using RHI.
This study will also determine whether human albumin 5% reduces plasma biomarkers of endothelial and glycocalyceal damage by measuring plasma concentrations of syndecan 1 and endocan at baseline (before surgery), and 1 and 24 hours following surgery. Blood samples will be taken on the morning of the surgery, within one hour of arrival to the intensive care unit (ICU), and 24 hours after surgery or within 2 hours before discharge from the ICU (three times altogether). These samples will be used to measure the plasma concentrations of two biomarkers that measure endothelial injury.
Detailed description
Cardiac surgical patients enrolled in the SHARP study will be randomized to 5% human albumin or 6% HES on entrance to the operating room. Anesthetic and Surgical management will follow protocol established by SHARP study including administration of a blinded study solution which contains 5% human albumin or 6% HES following separation from cardiopulmonary bypass. Blood will collected for measurement of baseline syndecan 1 and endocan following arterial line and urinary catheter placement before surgical incision. At 1 and 24 hrs following surgery completion, blood will be collected for measurement of syndecan 1 and endocan. Within two hours of ICU arrival, assessment of endothelial function will be performed.
In a subset of patients (patients who consent for multiple measurements), assessment of endothelial function will be performed preoperatively (baseline) and 24 hours after surgery.
Vasoactive substances may influence EndoPAT measurement. Thus the investigators will collect data on use of preoperative antihypertensive medications that have direct or indirect effect on arterial smooth muscle relaxation. Use of epinephrine, norepinephrine, vasopressin, milrinone, nitroglycerine, nitroprusside, and sedatives such as propofol, dexmedetomidine and others will be recorded and adjusted for in the analysis. Data on packed red blood cells (PRBC) and blood component transfusion will be collected from Anesthesia Record Keeping System. Indications for PRBC transfusion include hematocrit (HCT) <22% on cardiopulmonary bypass and <24% off cardiopulmonary bypass, and hypovolemia with anemia (HCT<25% with mean arterial blood pressure <60 mmHg or heart rate >100 bpm). Blood component transfusion (platelets, fresh frozen plasma, cryoprecipitate) may be administered as necessary following institutional standard of care. Imbalances in blood product transfusion between study groups will be adjusted for in the analysis.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Human albumin | Other | Drug: Human albuminHuman albumin 5% during surgery. |
| Hydroxyethyl starch | Other | Drug: Hydroxyethyl starchHydroxyethyl starch 6% (130/0.4) solution during surgery |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 40 - 85 years old
- Scheduled for elective aortic valve replacement with or without coronary artery bypass grafting with or without additional minor surgical procedure.
- Written, informed consent for participation in this investigation.
Key exclusion criteria (15 listed)
- Patients with Raynaud's disease or other disease associated with upper extremity vascular insufficiency,
- Inability to perform EndoPAT exam (inability to lie still for 15 min, or significant finger deformity),
- Patients with renal failure with oliguria or anuria not related to hypovolemia.
- Patients receiving dialysis.
- Patients with preoperative renal insufficiency (Creatinine > 1.6 mg/dL)
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 |
|---|---|---|
| Human albuminAlso: albuminhuman albumin 5% during surgery | Drug | Human albumin |
| Hydroxyethyl starchAlso: HES6% Hydroxyethyl starch 130/0.4 during surgery | Drug | Hydroxyethyl starch |
Primary outcome
Reactive Hyperemia Index (RHI)
Time frame: 2 hours after surgery
RHI measures endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT) with the EndoPAT device. It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered a sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. Increasing score indicates the improvement of coronary endothelial function.
2 secondary outcomes
Plasma Concentrations of Syndecan
Time frame: 1 hour after surgery, 24 hours after surgery
Plasma Concentrations of Endocan
Time frame: 1 hour after surgery, 24 hours after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Daniel Sessler, M.D. study chair
Department Chair
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Human albumin and Hydroxyethyl starch in people with Endothelial Dysfunction, run by The Cleveland Clinic 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 15 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 1 Feb 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2024). 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?
Reactive Hyperemia Index (RHI) (time frame: 2 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Feb 2024.