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

• ClinicalTrials.gov Identifier: NCT00060840
• Recruitment Status: Completed
• First Posted: May 15, 2003
• Results First Posted: September 17, 2010
• Last Update Posted: August 22, 2016
• Sponsor: Mallinckrodt
• Information provided by (Responsible Party): Mallinckrodt

Study Description

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

Condition or disease	Intervention/treatment	Phase
Congestive Heart Failure	Drug: Nitric Oxide; Drug: Nitrogen	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of Nitric Oxide for Inhalation During Left Ventricular Assist Device (LVAD) Implantation
• Study Start Date: July 2003
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: July 2008

Arms and Interventions

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 Name: INOmax
Placebo Comparator: Nitrogen; Nitrogen (N2) administered at 40 ppm.	Drug: Nitrogen; Nitrogen (N2) administered at 40 ppm for 48 hours

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 28 days ]

   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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, New Jersey

Newark Beth Isreal Medical Center

Newark, New Jersey, United States, 07112

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45219

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

United States, Texas

Baylor University Medical Center

Dallas, Texas, United States, 75226

University of Texas/St. Paul Medical Center

Dallas, Texas, United States, 75390

Texas Heart Institute

Houston, Texas, United States, 20345

Germany

Herz-und Diabeteszentrum Nordrhein-Westfalen

Gergstrab, Bad Oeynhausen, Germany, 32545

Deutsches Herfzzentrum Berlin

Augustenburger Platz, Berlin, Germany, 13353

United Kingdom

Harefield Hospital

Harefield, Middlesex, United Kingdom, UB96JH

Sponsors and Collaborators

Mallinckrodt

Investigators

• Study Director: James Baldassarre, MD; Mallinckrodt

More Information

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT00060840 History of Changes
• Other Study ID Numbers: INOT 41
• First Posted: May 15, 2003
• Results First Posted: September 17, 2010
• Last Update Posted: August 22, 2016
• Last Verified: July 2016

Keywords provided by Mallinckrodt:

Left Ventricular Assist Device Implantation; Progressive Left Ventricular Failure

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases; Nitric Oxide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters; Protective Agents