Clinical trial NCT00782652: The Effects of Nitric Oxide for Inhalation in Right Ventricular Infarction Patients
Official title: The Effects of Nitric Oxide for Inhalation on Survival or the Need for Dialysis or a Right Ventricular Assistance Device (RVAD) in Right Ventricular Infarction Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Right Ventricular Infarction
Keywords: myocaridal infarction
right ventricular infarction
cardiogenic shock
RVAD
Right ventricular assist device
cardiac disease
right ventricle
cardiac shock
heart dysfunction
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2008-10-31
Enrollment: 3
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: This study is designed to better understand the effects of nitric oxide, a gas for inhalation, on patients with right ventricular infarction.

Detailed description: This is a prospective, randomized, double-blind, placebo-controlled study that will assess the feasibility of studying inhaled nitric oxide for the treatment of cardiogenic shock due to right ventricular infarction, and the dose response of the acute hemodynamic changes occurring with nitric oxide inhalation in these patients. Patients with evidence of right ventricular infarction and cardiogenic shock, and have angiographic evidence of impaired blood flow to the right ventricle, or if right ventricular coronary perfusion is unimpared, cardiac shock persists, will be eligible for enrollment. Patients will receive standard of care for their condition, and will also recieve either nitric oxide for inhalation or placebo for up to 14 days.

Eligibility criteria: Inclusion Criteria:

* Acute inferior mycardial infarction (defined as an episode of chest pain lasting \>30 minutes and electrocardiographic evidence of 1 mm or greater ST elevation in inferior leads) within the past 72 hours.
* Invasive hemodynamic evidence of hemodynamically-significant RV dysfunction, defined as the presence of all the following: systemic venous congestion (mean RA pressure \> 10mmHg), the ratio of RA/PCW pressure 0.75 or greater, a low cardiac output as determined by Fick or Thermodilution (TD) technique (cardiac index \< 2.5 l/min/m2), systolic systemic arterial blood pressure of 90mmHg or less or requiring vasopressor or mechanical support to maintain systolic pressure \> 90mmHg. Patients with a PCWP of 14mmHg or less should receive intravascular volume repletion until their PCWP is \> 14mmHg.
* Coronary angiography revealing either an occlusion of the RCA proximal to any RV marginal branch or evidence of diminished flow to RV marginal branches of the RCA.
* If patient undergoes coronary revascularization, there must be evidence of unsuccessful right ventricular reperfusion (lack of restoration of TIMI grade III flow in the distal RCA and \> 1mm RV marginal branches) or evidence of hemodynamically significant RVI must persist for greater than 1 hour after successful revascularization.
* Age 18 years or greater

Exclusion Criteria:

* PCW 25mmHg or greater or mechanical complications of myocardial infarction requiring surgical correction.
* Severe LV systolic dysfunction as determined by the principal investigator. Unprotected left main coronary stenosis \> 50%.
* Pulmonary infiltrates consistent with pulonary edema on chest X-ray (if chest X-ray is clinically indicated).
* Evidence of shock-related end-organ damage, including creatinine 3.0 or greater, metabolic acidosis (pH 7.1 or less) and not corrected by 100 ml NaHCO3 (1mEq/ml), disseminated intravascular coagulation, or clinical evidence of diffuse brain injury.
* Previous history of severe pericardial, congenital, or valvular heart disease.
* Refractory hemodynamically significant arrhythmia.
* Presence of pneumonia, adult respiratory distress syndrome, or sepsis.
* Prior history of pulmonary disease requiring chronic oxygen therapy.
* Pregnancy
* Use of investigational drugs or device within the 30 days prior to enrollment to the study.
* Uncontrolled active bleeding.

Primary outcomes:
measure: survival to hospital discharge or Day 30, whichever occurs first without the need for renal replacement therapy or a Right Ventricular Assistance Device (RVAD)
timeFrame: hospital discharge or Day 30
Secondary outcomes:
measure: survival at 1 year after initial hospitalization
timeFrame: 1 year post treatment
measure: time on vasoconstrictor or inotropic medications
timeFrame: study duration
measure: duration of intraaortic balloon pump support, if applicable
timeFrame: study duration
measure: time in intensive care unit
timeFrame: study duration
measure: duration or need for mechanical ventilation
timeFrame: study duration
measure: change in cardiac index by dose
timeFrame: baseline, hour 8, days 3 & 7, and at day 30 or discharge
measure: change in right ventricule function and size by dose
timeFrame: baseline, hour 8, days 3 & 7 and at day 30 or discharge
measure: change in pulmonary vascular resistance by dose
timeFrame: study duration
measure: change in any right-to-left intracardiac shunt flow, as assessed by contrast echocardiography
timeFrame: study duration
measure: neurohormonal assessment of prognosis with BNP, NT-pro BNP
timeFrame: Baseline, hour 8 and days 3 & 7
measure: incidence of mortality
timeFrame: treatment duration through 1 year
measure: incidence and types of reported adverse events
timeFrame: study duration through day 30 or discharge
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg, University of Leuven
city: Ottawa
country: Canada
facility: Univeristy of Ottawa Heart Institute
state: Ontario
city: Alpejska
country: Poland
facility: Institute of Cardiology Warsaw
city: Barcelona
country: Spain
facility: Cardiovascular Department, Hospital Clinic
Study officials:
References: