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

Purpose

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/m2
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	Intervention	Phase
Congestive Heart Failure	Drug: Nitric Oxide Drug: placebo	Phase II

MedlinePlus related topics:

Heart Failure

Drug Information available for:

Nitric oxide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

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

Further study details as provided by INO Therapeutics:

Primary Outcome Measures:

The primary objective of the trial is to assess the utility of nitric oxide for inhalation for the management of acute right ventricular failure during LVAD placement. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment:	150
Study Start Date:	July 2003
Study Completion Date:	July 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Stratified based on the LVAD they receive (axial or pulsatile)	Drug: Nitric Oxide 40ppm of drug will be continuously administered at least 5 minutes prior to initiating the first weaning attempt from CPB
P: Placebo Comparator Stratified based on the LVAD they receive (axial or pulsatile)	Drug: placebo Open label investigational drug may be administered once a patient meets a minimum of two failure criteria or fails to wean at least once due to hemodynamic failure from cardiopulmonary bypass.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060840

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
	Cleveland Clinic Foundation
	Cleveland, Ohio, United States, 44195
	University of Cincinnati
	Cincinnati, Ohio, United States, 45219

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, Bad Oeynhausen
	Herz-und Diabeteszentrum Nordrhein-Westfalen
	Gergstrab, Bad Oeynhausen, Germany, 32545

Germany, Berlin
	Deutsches Herfzzentrum Berlin
	Augustenburger Platz, Berlin, Germany, 13353

United Kingdom, Middlesex
	Harefield Hospital
	Harefield, Middlesex, United Kingdom, UB96JH

Sponsors and Collaborators

INO Therapeutics

Investigators


Study Director:	James Baldassarre, MD	INO Therapeutics

More Information

Responsible Party:	INO Therapeutics ( Rob Small )
Study ID Numbers:	INOT 41
First Received:	May 14, 2003
Last Updated:	September 23, 2008
ClinicalTrials.gov Identifier:	NCT00060840
Health Authority:	United States: Food and Drug Administration

Keywords provided by INO Therapeutics:

Left Ventricular Assist Device Implantation

Progressive Left Ventricular Failure

Study placed in the following topic categories:

Nitric Oxide

Heart Failure

Heart Diseases

Additional relevant MeSH terms:

Respiratory System Agents

Vasodilator Agents

Neurotransmitter Agents

Antioxidants

Molecular Mechanisms of Pharmacological Action

Physiological Effects of Drugs

Anti-Asthmatic Agents

Cardiovascular Agents

Protective Agents

Pharmacologic Actions

Autonomic Agents

Therapeutic Uses

Free Radical Scavengers

Endothelium-Dependent Relaxing Factors

Cardiovascular Diseases

Peripheral Nervous System Agents

Bronchodilator Agents

ClinicalTrials.gov processed this record on November 18, 2008

Sponsored by:	INO Therapeutics
Information provided by:	INO Therapeutics
ClinicalTrials.gov Identifier:	NCT00060840