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

Congestive Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00060840
• Other study ID #: INOT 41
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2003
• Last updated: September 17, 2010
• Start date: July 2003
• Est. completion date: July 2008

Study information

• Verified date: September 2010
• Source: INO Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: July 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Nitric Oxide
40 ppm of Nitric Oxide continuously administered for 48 hours
• Nitrogen
Nitrogen (N2) administered at 40 ppm for 48 hours

Locations

Country	Name	City	State
Germany	Deutsches Herfzzentrum Berlin	Augustenburger Platz	Berlin
Germany	Herz-und Diabeteszentrum Nordrhein-Westfalen	Gergstrab	Bad Oeynhausen
United Kingdom	Harefield Hospital	Harefield	Middlesex
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Texas/St. Paul Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Texas Heart Institute	Houston	Texas
United States	Newark Beth Isreal Medical Center	Newark	New Jersey
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
INO Therapeutics

Countries where clinical trial is conducted

United States,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes