The Effects of Nitric Oxide for Inhalation During Left Ventricular Assists Device (LVAD) Implantation

NCT ID: NCT00060840

Last Updated: 2016-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2008-07-31

Brief Summary

The purpose of this study is to assess the utility of nitric oxide for inhalation during left ventricular assist device (LVAD) implantation following cardiopulmonary bypass (CPB). This is to be assessed by the number of patients in each treatment group meeting failure criteria within 24 hours on study drug, as defined by two or more of the following:

• Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m^2
• Administration of ≥ 20 inotropic equivalents (IE)

• 10 µg/kg/min dopamine, dobutamine, enoximone or amrinone is equivalent to 10 IE
• 0.1 µg/kg/min epinephrine or norepinephrine is equivalent to 10 IE
• 1 µg/kg/min milrinone is equivalent to 15 IE
• 0.1 U/min vasopressin is equivalent to 10 IE
• Mean arterial pressure (MAP) ≤ 55 mmHg
• Central venous pressure (CVP) ≥ 16 mmHg
• Percent mixed venous oxygen saturation (SvO2) ≤ 55%

Or at least one of the following criteria:

• Failure to wean from cardiopulmonary bypass at least once due to hemodynamic failure. Re-initiation of cardiopulmonary bypass to correct bleeding or other technical issues will not be considere 'failure to wean'
• Death

Detailed Description

40 ppm of either nitric oxide for inhalation or N2 (placebo) will be continuously administered to the patient starting at least 5 minutes prior to initiating the first weaning attempt from CPB and continue until the patient is either extubated, has reached failure criteria, or has been treated with study drug for 48 hours following discontinuation of CPB, whichever come first.

All patients will be monitored peri-operatively with a pulmonary arterial line, central venous line, and systemic arterial line. Baseline data collection by a designated clinical staff member will begin following induction of anesthesia and prior to skin incision. Following a successful wean from cardiopulmonary bypass, post-op data will be collected within 1 hour following end time of surgery. Data will then be collected at 6, 12, 18, 24, and 48 hours from post-op or until extubation, in which case weaning from study drug will begin.

Open label investigational nitric oxide for inhalation may be administered once a patient meets a minimum of two of the failure criteria or fails to wean at least once due to hemodynamic failure from cardiopulmonary bypass.

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Inhaled Nitric Oxide

Inhaled Nitric Oxide (iNO) at 40 parts per million (ppm)

Group Type: ACTIVE_COMPARATOR

Nitric Oxide

Intervention Type: DRUG

40 ppm of Nitric Oxide continuously administered for 48 hours

Nitrogen

Nitrogen (N2) administered at 40 ppm.

Group Type: PLACEBO_COMPARATOR

Nitrogen

Intervention Type: DRUG

Nitrogen (N2) administered at 40 ppm for 48 hours

Interventions

Nitric Oxide

40 ppm of Nitric Oxide continuously administered for 48 hours

Intervention Type: DRUG

Nitrogen

Nitrogen (N2) administered at 40 ppm for 48 hours

Intervention Type: DRUG

Other Intervention Names

INOmax

Eligibility Criteria

Inclusion Criteria

• Scheduled to undergo their first LVAD implantation, (or at least 6 months after explanation of a previous LVAD).
• Has a pulmonary vascular resistance of at least 2.5 Wood units (200 dynes/sec.) in the 30 days prior to LVAD placement.
• Greater than 18 years of age.
• Signed IRB approved informed consent.

Exclusion Criteria

• Patients with congestive heart failure due to giant cell myocarditis or restrictive cardiomyopathy.
• Elective Biventricular Assist Device (BiVAD) surgery, or current support with a temporary BiVad.
• LVAD procedure expected to be done without cardiopulmonary bypass.
• Pregnancy (a negative pregnancy test must be documented prior to enrollment).
• Received nitric oxide by inhalation therapy within the past 24 hours.
• Investigational drugs that are expected to change systemic or pulmonary vascular resistance are not allowed.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mallinckrodt

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Baldassarre, MD

Role: STUDY_DIRECTOR

Mallinckrodt

Locations

Newark Beth Isreal Medical Center

Newark, New Jersey, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Baylor University Medical Center

Dallas, Texas, United States

University of Texas/St. Paul Medical Center

Dallas, Texas, United States

Texas Heart Institute

Houston, Texas, United States

Herz-und Diabeteszentrum Nordrhein-Westfalen

Gergstrab, Bad Oeynhausen, Germany

Deutsches Herfzzentrum Berlin

Augustenburger Platz, State of Berlin, Germany

Harefield Hospital

Harefield, Middlesex, United Kingdom

Countries

United States; Germany; United Kingdom

Other Identifiers

INOT 41

Identifier Type: -

Identifier Source: org_study_id