The Effects of Nitric Oxide for Inhalation in Right Ventricular Infarction Patients

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

This study is designed to better understand the effects of nitric oxide, a gas for inhalation, on patients with right ventricular infarction.

Study Overview

• Status: Terminated
• Conditions: Right Ventricular Infarction
• Intervention / Treatment: Drug: inhaled nitric oxide; Drug: nitrogen gas

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • University Hospital Gasthuisberg, University of Leuven
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Univeristy of Ottawa Heart Institute
• Poland
  • Alpejska, Poland, 42
    • Institute of Cardiology Warsaw
• Spain
  • Barcelona, Spain, 08036
    • Cardiovascular Department, Hospital Clinic
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; inhaled nitric oxide at 40 or 80ppm	Drug: inhaled nitric oxide; Continuous delivery at either 40 or 80 ppm for a duration of up to 14 days; Other Names: INOmax
Placebo Comparator: 2; inhaled nitrogen at either 40 or 80ppm	Drug: nitrogen gas; Continuous delivery at either 40 or 80 ppm for a duration of up to 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
survival to hospital discharge or Day 30, whichever occurs first without the need for renal replacement therapy or a Right Ventricular Assistance Device (RVAD)	hospital discharge or Day 30

Secondary Outcome Measures

Outcome Measure	Time Frame
survival at 1 year after initial hospitalization	1 year post treatment
time on vasoconstrictor or inotropic medications	study duration
duration of intraaortic balloon pump support, if applicable	study duration
time in intensive care unit	study duration
duration or need for mechanical ventilation	study duration
change in cardiac index by dose	baseline, hour 8, days 3 & 7, and at day 30 or discharge
change in right ventricule function and size by dose	baseline, hour 8, days 3 & 7 and at day 30 or discharge
change in pulmonary vascular resistance by dose	study duration
change in any right-to-left intracardiac shunt flow, as assessed by contrast echocardiography	study duration
neurohormonal assessment of prognosis with BNP, NT-pro BNP	Baseline, hour 8 and days 3 & 7
incidence of mortality	treatment duration through 1 year
incidence and types of reported adverse events	study duration through day 30 or discharge

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 29, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Estimate): September 9, 2016
• Last Update Submitted That Met QC Criteria: September 8, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: cardiogenic shock; right ventricle; myocaridal infarction; right ventricular infarction; RVAD; Right ventricular assist device; cardiac disease; cardiac shock; heart dysfunction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: INOT43