Clinical trial NCT00060840: The Effects of Nitric Oxide for Inhalation During Left Ventricular Assists Device (LVAD) Implantation
Official title: The Effects of Nitric Oxide for Inhalation During Left Ventricular Assist Device (LVAD) Implantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congestive Heart Failure
Keywords: Left Ventricular Assist Device Implantation
Progressive Left Ventricular Failure
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2003-05-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: 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.
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Newark
country: United States
facility: Newark Beth Isreal Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas/St. Paul Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Gergstrab
country: Germany
facility: Herz-und Diabeteszentrum Nordrhein-Westfalen
state: Bad Oeynhausen
city: Augustenburger Platz
country: Germany
facility: Deutsches Herfzzentrum Berlin
state: Berlin
city: Harefield
country: United Kingdom
facility: Harefield Hospital
state: Middlesex
Study officials:
affiliation: Mallinckrodt
name: James Baldassarre, MD
role: STUDY_DIRECTOR
References: