HypertensionPhase 2SPRINTNCT00799604
Clevidipine Bolus Administration in the Treatment of Hypertensive Patients Undergoing Cardiac Surgery (SPRINT)
A Phase 2 study testing clevidipine in people with Hypertension, run by The Medicines Company at 2 sites in United States.
Trial summary
This study was designed to evaluate the pharmacodynamics of a bolus dosing regimen of clevidipine, a vascular-selective L-type calcium channel antagonist, for the management of blood pressure in cardiac surgery patients, as well as to evaluate the efficacy, safety and pharmacokinetics of clevidipine after bolus… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- clevidipine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2008to Oct 2009
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Require elective cardiac operation involving the use of cardiopulmonary bypass
- Age 18 years or older
- A history or hypertension and/or expected to require perioperative antihypertensive therapy in the opinion of the investigator
- Written informed consent
- Pre-anesthesia baseline SBP ≥140 mm Hg just prior to bolus, measured using an arterial line
Who cannot join
- Receiving either intravenous vasopressor or intravenous vasodilatory therapy in the 72 hours prior to dosing
- Critical left main coronary artery stenosis
- Critical aortic valve (<0.5 cm3) or mitral valve (<1.0 cm3) stenosis
- Acute myocardial infarction within the prior 14 days
- Fully paced cardiac rhythm
- Known or suspected aortic dissection
Show all 13Show fewer
- Requiring preoperative intra-aortic balloon pump counterpulsation therapy
- Contraindication to transesophageal echocardiography
- Positive pregnancy test or breast feeding
- Intolerance or allergy to calcium channel blockers
- Allergy to soybean oil or egg lecithin
- Any condition(s) that in the Investigator's opinion would warrant exclusion from the study or prevent the patient from completing the study
- Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital, Harvard Medical School
Boston, Massachusetts, 02114
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: An Open-label Study in Patients Undergoing Cardiac Surgery to Evaluate the Effect of Bolus Clevidipine Administration (SPRINT)
This study was designed to evaluate the pharmacodynamics of a bolus dosing regimen of clevidipine, a vascular-selective L-type calcium channel antagonist, for the management of blood pressure in cardiac surgery patients, as well as to evaluate the efficacy, safety and pharmacokinetics of clevidipine after bolus administration.
Read the detailed description
Study participants were screened up to 14 days prior to their elective cardiac surgery. For the purpose of this study, hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg immediately prior to initiation of study drug.
On the day of surgery, an IV bolus dose of clevidipine (Bolus 1 - pre-anesthesia) was administered to each eligible study participant during Treatment Period 1 to decrease BP before induction of general anesthesia. The dose (either 125 μg, 250 μg or 500 μg) given was based on the assigned cohort for each participant, listed in the 'Arms' section below.
At the discretion of the investigator, a second IV bolus dose of clevidipine (Bolus 2 - with anesthesia) could have been administered during Treatment Period 2 at either 125 μg, 250 μg or 500 μg, based upon the earlier observed response to Bolus 1. This dose was administered after the induction of anesthesia, to decrease BP prior to cannulation of the ascending aorta for initiation of cardiopulmonary bypass.
Assessment of safety was performed throughout Treatment Periods 1 and 2 with Adverse Events (AEs) followed 6 hours post final bolus dose and Serious Adverse Events (SAEs) followed 24 hours post final bolus dose.
- Conditions
- Hypertension
- Being tested
- clevidipine
- Keywords
- Hypertension, Antihypertensive Agent, Calcium Channel Blocker
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clevidipineDrug
Also called clevidipine injectable emulsion, clevidipine emulsion, Cleviprex
Clevidipine (0.5mg/mL in 20% lipid emulsion) was administered as an IV bolus (<5 sec) by rapid injection for Bolus 1 and for Bolus 2, if second bolus dose was administered, directly into a peripheral venous catheter followed by a normal saline flush (10mL).
| Study group | Role | What they receive |
|---|---|---|
| clevidipine | Experimental | Patients were sequentially assigned to one of following three planned dose cohorts for Bolus 1 within the clevidipine arm:
* Cohort 1: clevidipine 250 µg (0.5 mL)
* Cohort 2: clevidipine 500 µg (1 mL)
* Cohort 3: clevidipine 125 µg (0.25 mL or 0.5 mL of a 1:1 solution) Receives: Drug: clevidipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Mean Maximum Absolute Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum absolute change is the minimum SBP value within 15 minutes from bolus 1 minus baseline value.
Measured: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
The Mean Maximum Percent Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum percent change is defined as the maximum absolute change divided by the baseline value of bolus 1 and multiplied by 100.
Measured: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Secondary outcomes (5)
The Percentage of Patients With Systolic Blood Pressure ≤85 mm Hg Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
The percentage is calculated using the number of patients with a systolic blood pressure ≤85 mm Hg within 15 minutes from the initial Bolus 1 dose divided by the total number of patients who were treated with a Bolus 1 clevidipine, and multiplied by 100.
Measured: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
The Median Time to 5%, 10%, and 15% Systolic Blood Pressure Reduction From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 -Pre-anesthesia).
BP was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of bolus 1 is defined as median of all measurements prior to or at the start of Bolus 1. The time at which first target SBP reduction (ex. 5%) from baseline was reached was identified for each patient using fitted values from LOWESS method. Kaplan-Meier method was used to estimate the median time. Patients who never reached 5%, 10% or 15% reduction, withdrew from study or changed antihypertensive within 15 minutes were censored.
Measured: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
The Mean Percent Change in Systolic Blood Pressure From Baseline Over Time During the First 15 Minutes Following First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
BP was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as median of all measurements prior to or at the start of Bolus 1. SBP change (percent change) from baseline is calculated at each collection time point after bolus 1 dose for each patient.
Measured: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
The Median Time to 50%, and, When Available, 90% Recovery From Maximum SBP Effect Following the First Bolus Dose of Clevidipine for Patients Who Achieved the Endpoints (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Analysis is of the time in minutes between the recorded time at the maximum absolute change and the time of the systolic blood pressure value at the first 50% recovery. The 50% recovery value is equal to the minimum recorded systolic blood pressure value plus 50% of the maximum amount of systolic blood pressure reduction (the Bolus 1 baseline value minus the value at the maximum absolute change).
Measured: Up to 15 minutes following the first bolus dose of clevidipine (pre-anesthesia).
Change in Heart Rate After Bolus 1 (Pre-anesthesia).
The baseline heart rate was measured as the median of all the heart rate measurements within 60 seconds or at the start of the administration of Bolus 1.
Measured: Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionOct 2009
- Study completionOct 2009
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 HypertensionStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Medicines Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Albert T. Cheung, MD, Principal investigator, University of PennsylvaniaEdwin G. Avery, IV, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00799604
- Sponsor's protocol ID
- TMC-CLV-08-02
- Acronym
- SPRINT
- Status last verified
- Aug 2014
- First submitted
- 26 Nov 2008
- Last updated
- 29 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study in Patients Undergoing Cardiac Surgery to Evaluate the Effect of Bolus Clevidipine Administration (SPRINT)
- ClinicalTrials.gov ID
- NCT00799604
- Acronym / sponsor ID
- SPRINT / TMC-CLV-08-02
- Conditions
- Hypertension
- Keywords
- Hypertension, Antihypertensive Agent, Calcium Channel Blocker
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- The Medicines CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 1 Dec 2008 (estimated)
- Results
- Posted 4 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was designed to evaluate the pharmacodynamics of a bolus dosing regimen of clevidipine, a vascular-selective L-type calcium channel antagonist, for the management of blood pressure in cardiac surgery patients, as well as to evaluate the efficacy, safety and pharmacokinetics of clevidipine after bolus administration.
Detailed description
Study participants were screened up to 14 days prior to their elective cardiac surgery. For the purpose of this study, hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg immediately prior to initiation of study drug.
On the day of surgery, an IV bolus dose of clevidipine (Bolus 1 - pre-anesthesia) was administered to each eligible study participant during Treatment Period 1 to decrease BP before induction of general anesthesia. The dose (either 125 μg, 250 μg or 500 μg) given was based on the assigned cohort for each participant, listed in the 'Arms' section below.
At the discretion of the investigator, a second IV bolus dose of clevidipine (Bolus 2 - with anesthesia) could have been administered during Treatment Period 2 at either 125 μg, 250 μg or 500 μg, based upon the earlier observed response to Bolus 1. This dose was administered after the induction of anesthesia, to decrease BP prior to cannulation of the ascending aorta for initiation of cardiopulmonary bypass.
Assessment of safety was performed throughout Treatment Periods 1 and 2 with Adverse Events (AEs) followed 6 hours post final bolus dose and Serious Adverse Events (SAEs) followed 24 hours post final bolus dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| clevidipine | Experimental | Drug: clevidipinePatients were sequentially assigned to one of following three planned dose cohorts for Bolus 1 within the clevidipine arm: * Cohort 1: clevidipine 250 µg (0.5 mL) * Cohort 2: clevidipine 500 µg (1 mL) * Cohort 3: clevidipine 125 µg (0.25 mL or 0.5 mL of a 1:1 solution) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Require elective cardiac operation involving the use of cardiopulmonary bypass
- Age 18 years or older
- A history or hypertension and/or expected to require perioperative antihypertensive therapy in the opinion of the investigator
- Written informed consent
- Pre-anesthesia baseline SBP ≥140 mm Hg just prior to bolus, measured using an arterial line
Key exclusion criteria (13 listed)
- Receiving either intravenous vasopressor or intravenous vasodilatory therapy in the 72 hours prior to dosing
- Critical left main coronary artery stenosis
- Critical aortic valve (<0.5 cm3) or mitral valve (<1.0 cm3) stenosis
- Acute myocardial infarction within the prior 14 days
- Fully paced cardiac rhythm
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 |
|---|---|---|
| clevidipineAlso: clevidipine injectable emulsion, clevidipine emulsion, CleviprexClevidipine (0.5mg/mL in 20% lipid emulsion) was administered as an IV bolus (<5 sec) by rapid injection for Bolus 1 and for Bolus 2, if second bolus dose was administered, directly into a peripheral venous catheter followed by a normal saline flush (10mL). | Drug | clevidipine |
Primary outcome
The Mean Maximum Absolute Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum absolute change is the minimum SBP value within 15 minutes from bolus 1 minus baseline value.
The Mean Maximum Percent Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum percent change is defined as the maximum absolute change divided by the baseline value of bolus 1 and multiplied by 100.
5 secondary outcomes
The Percentage of Patients With Systolic Blood Pressure ≤85 mm Hg Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
The Median Time to 5%, 10%, and 15% Systolic Blood Pressure Reduction From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 -Pre-anesthesia).
Time frame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
The Mean Percent Change in Systolic Blood Pressure From Baseline Over Time During the First 15 Minutes Following First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Time frame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
The Median Time to 50%, and, When Available, 90% Recovery From Maximum SBP Effect Following the First Bolus Dose of Clevidipine for Patients Who Achieved the Endpoints (Treatment Period 1, Bolus 1 - Pre-anesthesia).
Time frame: Up to 15 minutes following the first bolus dose of clevidipine (pre-anesthesia).
Change in Heart Rate After Bolus 1 (Pre-anesthesia).
Time frame: Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Albert T. Cheung, MD principal investigator
University of Pennsylvania
Edwin G. Avery, IV, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing clevidipine in people with Hypertension, run by The Medicines Company at 2 sites 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 13 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 29 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2014). 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?
The Mean Maximum Absolute Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia). (time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).). The study lists 2 primary outcomes in all. 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 29 Aug 2014.