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

NCT00060840 | Completed Phase 2 Results DMC

• 1 other identifier: INOT 41
• Study Type: interventional
• Target: 150
• Locations: 3 countries
• Sites: 11

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

Conditions

Congestive Heart Failure

Keywords

Left Ventricular Assist Device Implantation; Progressive Left Ventricular Failure

Outcome Measures

Primary Outcomes (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.

  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

Study Arms (2)

Inhaled Nitric Oxide

ACTIVE COMPARATOR

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

Drug: Nitric Oxide

Nitrogen

PLACEBO COMPARATOR

Nitrogen (N2) administered at 40 ppm.

Drug: Nitrogen

Interventions

Nitric Oxide DRUG

40 ppm of Nitric Oxide continuously administered for 48 hours

Also known as: INOmax

Inhaled Nitric Oxide

Nitrogen DRUG

Nitrogen (N2) administered at 40 ppm for 48 hours

Nitrogen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (11)

Newark Beth Isreal Medical Center

Newark, New Jersey, 07112, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Baylor University Medical Center

Dallas, Texas, 75226, United States

Location

University of Texas/St. Paul Medical Center

Dallas, Texas, 75390, United States

Location

Texas Heart Institute

Houston, Texas, 20345, United States

Location

Herz-und Diabeteszentrum Nordrhein-Westfalen

Gergstrab, Bad Oeynhausen, 32545, Germany

Location

Deutsches Herfzzentrum Berlin

Augustenburger Platz, State of Berlin, 13353, Germany

Location

Harefield Hospital

Harefield, Middlesex, UB96JH, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Nitric Oxide; Endothelium-Dependent Relaxing Factors; Nitrogen

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Elements; Gases

Results Point of Contact

• Title: Lawrence Hill
• Organization: Mallinckrodt

lawrence.hill@mallinckrodt.com

908-238-6370

Study Officials

• James Baldassarre, MD

  Mallinckrodt

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2003
• First Posted: May 15, 2003
• Study Start: July 1, 2003
• Primary Completion: June 1, 2008
• Study Completion: July 1, 2008
• Last Updated: August 22, 2016
• Results First Posted: September 17, 2010

Record last verified: 2016-07

Locations

GB (1); US (8); DE (2)