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

Mallinckrodt

Status and phase

Completed

Phase 2

Conditions

Congestive Heart Failure

Treatments

Drug: Nitric Oxide

Drug: Nitrogen

Study type

Interventional

Funder types

Industry

Identifiers

NCT00060840

INOT 41

Details and patient eligibility

About

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

Full 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.

Enrollment

150 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.