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

Primary Purpose

Right Ventricular Infarction

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
inhaled nitric oxide
nitrogen gas
Sponsored by
Mallinckrodt
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Right Ventricular Infarction focused on measuring myocaridal infarction, right ventricular infarction, cardiogenic shock, RVAD, Right ventricular assist device, cardiac disease, right ventricle, cardiac shock, heart dysfunction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Massachusetts General Hospital
  • William Beaumont Hospital
  • University Hospital Gasthuisberg, University of Leuven
  • Univeristy of Ottawa Heart Institute
  • Institute of Cardiology Warsaw
  • Cardiovascular Department, Hospital Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

inhaled nitric oxide at 40 or 80ppm

inhaled nitrogen at either 40 or 80ppm

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

survival at 1 year after initial hospitalization
time on vasoconstrictor or inotropic medications
duration of intraaortic balloon pump support, if applicable
time in intensive care unit
duration or need for mechanical ventilation
change in cardiac index by dose
change in right ventricule function and size by dose
change in pulmonary vascular resistance by dose
change in any right-to-left intracardiac shunt flow, as assessed by contrast echocardiography
neurohormonal assessment of prognosis with BNP, NT-pro BNP
incidence of mortality
incidence and types of reported adverse events

Full Information

First Posted
October 29, 2008
Last Updated
September 8, 2016
Sponsor
Mallinckrodt
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1. Study Identification

Unique Protocol Identification Number
NCT00782652
Brief Title
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

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
Slow enrollment
Study Start Date
March 2006 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
February 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mallinckrodt

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Right Ventricular Infarction
Keywords
myocaridal infarction, right ventricular infarction, cardiogenic shock, RVAD, Right ventricular assist device, cardiac disease, right ventricle, cardiac shock, heart dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
inhaled nitric oxide at 40 or 80ppm
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
inhaled nitrogen at either 40 or 80ppm
Intervention Type
Drug
Intervention Name(s)
inhaled nitric oxide
Other Intervention Name(s)
INOmax
Intervention Description
Continuous delivery at either 40 or 80 ppm for a duration of up to 14 days
Intervention Type
Drug
Intervention Name(s)
nitrogen gas
Intervention Description
Continuous delivery at either 40 or 80 ppm for a duration of up to 14 days
Primary Outcome Measure Information:
Title
survival to hospital discharge or Day 30, whichever occurs first without the need for renal replacement therapy or a Right Ventricular Assistance Device (RVAD)
Time Frame
hospital discharge or Day 30
Secondary Outcome Measure Information:
Title
survival at 1 year after initial hospitalization
Time Frame
1 year post treatment
Title
time on vasoconstrictor or inotropic medications
Time Frame
study duration
Title
duration of intraaortic balloon pump support, if applicable
Time Frame
study duration
Title
time in intensive care unit
Time Frame
study duration
Title
duration or need for mechanical ventilation
Time Frame
study duration
Title
change in cardiac index by dose
Time Frame
baseline, hour 8, days 3 & 7, and at day 30 or discharge
Title
change in right ventricule function and size by dose
Time Frame
baseline, hour 8, days 3 & 7 and at day 30 or discharge
Title
change in pulmonary vascular resistance by dose
Time Frame
study duration
Title
change in any right-to-left intracardiac shunt flow, as assessed by contrast echocardiography
Time Frame
study duration
Title
neurohormonal assessment of prognosis with BNP, NT-pro BNP
Time Frame
Baseline, hour 8 and days 3 & 7
Title
incidence of mortality
Time Frame
treatment duration through 1 year
Title
incidence and types of reported adverse events
Time Frame
study duration through day 30 or discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
William Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
University Hospital Gasthuisberg, University of Leuven
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Univeristy of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
Institute of Cardiology Warsaw
City
Alpejska
ZIP/Postal Code
42
Country
Poland
Facility Name
Cardiovascular Department, Hospital Clinic
City
Barcelona
ZIP/Postal Code
08036
Country
Spain

12. IPD Sharing Statement

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

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