Clevidipine for Vasoreactivity Evaluation of the Pulmonary Arterial Bed (CARVE)

• ClinicalTrials.gov Identifier: NCT01121458
• Recruitment Status: Completed
• First Posted: May 12, 2010
• Last Update Posted: June 10, 2013
• Sponsor: North Texas Veterans Healthcare System
• Information provided by (Responsible Party): Subhash Banerjee, North Texas Veterans Healthcare System

Tracking Information

• First Submitted Date: February 2, 2010
• First Posted Date: May 12, 2010
• Last Update Posted Date: June 10, 2013
• Study Start Date: September 2009
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 10, 2010): Percent reduction in PVR with clevidipine in (1) nitroprusside responders and (2) patients with indeterminate nitroprusside reactivity tests [ Time Frame: During right heart catheterization (1-2 hours) ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: May 10, 2010): Efficacy/ safety measured by % reduction in PVR with clevidipine in patients with indeterminate reactivity tests & total study population;%patients with successful 20% reduction in PVR; SAE & adverse hemodynamic response to clevidipine during procedure [ Time Frame: During right heart catheterization (1-2 hrs) ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clevidipine for Vasoreactivity Evaluation of the Pulmonary Arterial Bed
• Official Title: Clevidipine for Vasoreactivity Evaluation of the Pulmonary Arterial Bed (CARVE)

Brief Summary

Pulmonary arterial hypertension (PAH) is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (PA) rises above normal levels and may become life threatening. PAH is frequently misdiagnosed and has often progressed to late stage by the time it is accurately diagnosed. PAH has been historically chronic and incurable with a poor survival rate. However, new treatments are available which have significantly improved prognosis. Right-heart catheterization (RHC) is the most accurate and useful test for PAH, and the only test that directly measures the pressure inside the PA. It is performed in all patients at least once, to get a definitive diagnosis of PAH.

The most commonly used medication for this purpose is intravenous nitroprusside, however this medication in about 25-30% of patients is not well tolerated as it cause fast heart rates, which is not well tolerated by patients with pulmonary hypertension and/or heart failure. The CARVE study assesses the effect of Clevidipine, an ultra-short acting vasoselective calcium antagonist, on pulmonary vascular resistance (PVR) and its utility for pulmonary vasoreactivity testing during right heart catheterization (RHC) of patients with pulmonary hypertension (PAH).

Detailed Description

CARVE is a Phase 4 open-label descriptive observational trial in PAH patients undergoing invasive vasoreactivity testing in the cath lab at the Dallas VA Medical Center. Patients clinically indicated for RHC and assessment of pulmonary artery vasoreactivity will be enrolled if they meet the inclusion/exclusion criteria. The study will involve the following tests:

1. Performance of clinically indicated RHC with assessment of pulmonary hypertension and pulmonary vascular resistance (PVR).
2. Performance of clinically indicated pulmonary vasoreactivity assessment with IV Nitroprusside (standard of care)
3. For patients who are responsive to Nitroprusside, or those who have an inconclusive result because of intolerability to Nitroprusside, pulmonary vasoreactivity assessment with study drug (IV) will be conducted.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Hypertension, Pulmonary

Intervention

Drug: Clevidipine

The clevidipine infusion is to be administered via IV infusion at a starting dose of 0.5 mg/hour. The dose may be doubled every three (3) minutes to a maximum dose of 32 mg/hr as tolerated, until a 20% reduction in PVR is achieved or until the patient experiences hypotension (SBP< 80 mmHg), hypertension (SBP>150 mmHg), tachycardia (120 beats per minute), bradycardia (<50 beats per minute), or symptoms of hypotension or ischemia (chest pain, anxiety, nausea, vomiting), allergic reaction (hives, urticaria) or other adverse event. Clevidipine infusion may be terminated at any time for a safety reason or at the investigator's discretion.

Other Name: Cleviprex

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 7, 2013): 12
• Original Estimated Enrollment (submitted: May 10, 2010): 20
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Provide written informed consent before initiation of any study related procedures.
• 21 years of age or older
• Referred for clinically indicated pulmonary vascular resistance assessment
• Presence of pulmonary hypertension by non-invasive testing
• Patients referred for RHC and vasoreactivity testing

Exclusion Criteria:

• Patient with baseline SBP < 100 mmHg
• Patient with HR>120 beats/minute
• Patients with severe or valvular heart disease
• Patients with an acute coronary syndrome
• Patients with a creatinine clearance < 30 ml/min
• Patients with class IV congestive heart failure
• Patients with platelet count < 100,000 per cc3
• Patients with hemoglobin < 10g/dl
• Patient with INR > 1.5
• Patients with positive pregnancy test - women between 21 and 60 years of age
• Patients with known or suspected allergy to study drug or study drug components, including allergy to soybeans, soy products, eggs, or egg products
• Patients with defective lipid metabolism such as pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if it is accompanied by hyperlipidemia
• Patients with contraindications to the use of IV nitroprusside
• Patients with diagnosed or suspected intra-cardiac or systemic arteriovenous shunts
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 3 months of randomization.
• Other medical conditions that, in the opinion of the investigator, preclude participation in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01121458
• Other Study ID Numbers: Dallas VA #09-041
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Subhash Banerjee, North Texas Veterans Healthcare System
• Original Responsible Party: Subhash Banerjee,MD, VA North Texas Health Care System
• Current Study Sponsor: North Texas Veterans Healthcare System
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Subhash Banerjee, MD; North Texas Veterans Healthcare System

• PRS Account: North Texas Veterans Healthcare System
• Verification Date: June 2013