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

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

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

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Drug: Nitric Oxide; Drug: Nitrogen

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bad Oeynhausen
    • Gergstrab, Bad Oeynhausen, Germany, 32545
      • Herz-und Diabeteszentrum Nordrhein-Westfalen
  • Berlin
    • Augustenburger Platz, Berlin, Germany, 13353
      • Deutsches Herfzzentrum Berlin
• United Kingdom
  • Middlesex
    • Harefield, Middlesex, United Kingdom, UB96JH
      • Harefield Hospital
• United States
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Isreal Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75390
      • University of Texas/St. Paul Medical Center
    • Houston, Texas, United States, 20345
      • Texas Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inhaled Nitric Oxide; Inhaled Nitric Oxide (iNO) at 40 parts per million (ppm)	Drug: Nitric Oxide; 40 ppm of Nitric Oxide continuously administered for 48 hours; Other Names: INOmax
Placebo Comparator: Nitrogen; Nitrogen (N2) administered at 40 ppm.	Drug: Nitrogen; Nitrogen (N2) administered at 40 ppm for 48 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Subjects With Left Ventricular Failure During Left Ventricular Assistance Device (LVAD) Placement After Cardio Pulmonary Bypass, as Determined by Failure Criteria, After Administration of Nitric Oxide.	Failure criteria used to measure outcome includes: Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m^2; Administration of ≥ 20 inotropic equivalents (IE); Mean arterial pressure (MAP) ≤ 55 mm Hg; Central venous pressure (CVP) ≥ 16 mm Hg; Percentage of mixed venous oxygen saturation (SvO2) of ≤ 55% OR failure to wean from cardio pulmonary bypass (CPB) at least once due to hemodynamic failure or death.	28 days

Collaborators and Investigators

• Sponsor: Mallinckrodt
• Investigators: Study Director: James Baldassarre, MD, Mallinckrodt

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: May 14, 2003
• First Submitted That Met QC Criteria: May 14, 2003
• First Posted (Estimate): May 15, 2003

Study Record Updates

• Last Update Posted (Estimate): August 22, 2016
• Last Update Submitted That Met QC Criteria: July 22, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Left Ventricular Assist Device Implantation; Progressive Left Ventricular Failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: INOT 41