Clevidipine for Vasoreactivity Evaluation of the Pulmonary Arterial Bed

Hypertension, Pulmonary Clinical Trial

— CARVE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01121458
• Other study ID #: Dallas VA #09-041
• Status: Completed
• Phase: Phase 4
• First received: February 2, 2010
• Last updated: June 7, 2013
• Start date: September 2009
• Est. completion date: April 2013

Study information

• Verified date: June 2013
• Source: North Texas Veterans Healthcare System
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• 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.

Locations

Country	Name	City	State
United States	VA North Texas Health Care System	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
North Texas Veterans Healthcare System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent reduction in PVR with clevidipine in (1) nitroprusside responders and (2) patients with indeterminate nitroprusside reactivity tests		During right heart catheterization (1-2 hours)	No
Secondary	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		During right heart catheterization (1-2 hrs)	Yes