Nitric Oxide in Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO) (NOVICE)

Nitric Oxide in Right Ventricular Dysfunction: Improvements in Clinical and Hemodynamic Parameters on Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO; NOVICE)

This pilot study is designed to investigate the effect of inhaled nitric oxide on cardiac, pulmonary artery, and systemic hemodynamics at various time points during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Patients who have been initiated on VA-ECMO will be invited to participate. Inhaled nitric oxide (iNO) will be used early after VA-ECMO cannulation (once consent is obtained). After baseline hemodynamic, biochemical, and echocardiographic parameters are assessed, iNO will be initiated and all parameters will be reassessed after 30 minutes and 6 hours. Inhaled nitric oxide will then be discontinued and all parameters repeated. At the time of VA-ECMO weaning (timing determined by clinical team), iNO will be reinitiated with repeat assessment of hemodynamic, biochemical, and echocardiographic parameters both prior to the wean and after the wean (whether successful or not).

Study Overview

• Status: Unknown
• Conditions: Extracorporeal Membrane Oxygenation; Shock, Cardiogenic; Nitric Oxide
• Intervention / Treatment: Drug: Inhaled nitric oxide

Detailed Description

This is a proof of concept, pilot, phase II study using iNO in patients on VA-ECMO. Stage 1 will assess the participant's response to iNO early after cannulation. Stage 2 will assess the participant's response to iNO during the ECMO weaning process.

Stage 1 Patients in whom VA-ECMO is being initiated will be invited to participate. Hemodynamic, echocardiographic, and biochemical parameters will be measured immediately prior to iNO administration and repeated 30 minutes after iNO initiation. iNO will be continued for six hours to allow hemodynamic and oxygenation parameters to stabilize as per previous protocols in the literature. After six hours, hemodynamic, echocardiographic, and biochemical parameters will be re-assessed after which iNO will be discontinued. All parameters will be re-evaluated 30 minutes after iNO discontinuation.

Stage 2 A weaning trial will be performed at 1) the earliest signs of myocardial recovery or b) day 5. Myocardial recovery will be defined as: mean arterial pressure > 60 millimeters of mercury (mmHg) on no or minimal inotropic/vasopressor support, arterial pulse pressure > 10 mmHg, and minimal respiratory support (oxygen saturation > 88% on < 2 liters by nasal cannulae, or minimal ventilator setting if intubated). Inhaled nitric oxide will be re-initiated 30 minutes prior to the ECMO weaning trial. Adequacy of perfusion will be defined as a mixed venous oxygen saturation of > 70%. Hemodynamic, echocardiographic, and biochemical parameter will be recorded immediately prior to iNO administration and then at 30 minutes prior to the ECMO weaning trial. ECMO will be weaned as per the standard protocol at the University Health Network with re-assessment of all parameters after weaning is complete. When ECMO weaning is unsuccessful, these parameters will be recorded immediately prior to re-initiation of full flow VA-ECMO and 30 minutes thereafter. VA-ECMO weaning will be re-attempted at 24-48 hours at the discretion of the medical team.

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2C4
      • Recruiting
      • Toronto General Hospital
      • Contact: Katherine Tsang, RN BScN; Phone Number: 14163403280; Email: katherine.tsang@uhn.ca
      • Contact: Andrea Daly, MD; Phone Number: 16475457454; Email: andrealdaly@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will be comprised of participants with decompensated heart failure in whom VA ECMO is being used as a bridge to recovery, cardiac transplantation, or durable mechanical circulatory support (MCS).

Description

Inclusion Criteria:

• Age>18years
• History or evidence of left ventricular failure

Exclusion Criteria:

• ECMO cannulation site other than the femoral vein and artery
• Insufficient echocardiographic images to assess ventricular function
• Right ventricular assist device
• Uncorrected congenital heart disease
• Primary graft failure
• No cardiac output on bedside ECHO (LVEF<5%)
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Inhaled nitric oxide

Drug: Inhaled nitric oxide; Stage 1: Patients in whom VA ECMO is being initiated will be invited to participate. Hemodynamic, echocardiographic, and biochemical parameters will be measured immediately prior to iNO administration, and thirty minutes after initiation. After six hours, hemodynamic, echocardiographic, and biochemical parameters will be re-assessed after which iNO will be weaned. All parameters will be re-evaluated 30 minutes after iNO discontinuation. Stage 2: iNO will be re-initiated 30 minutes prior to the ECMO weaning trial. Hemodynamic, echocardiographic, and biochemical parameter will be recorded immediately prior to iNO administration and then at 30 minutes prior to the ECMO weaning trial. When ECMO weaning is unsuccessful, these parameters will be recorded immediately prior to re-initiation of full flow VA ECMO and 30 minutes thereafter. If successful, data will be collected after the wean and after iNO discontinuation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant recruitment	Recruitment of ten participants	February 2020
Right Heart - Qualitative function, change from baseline	Mild/moderate/severe dysfunction as determined by reading echocardiographer	After 6 hours of inhaled nitric oxide
Right Heart - Tricuspid annular plane systolic excursion (TAPSE), change from baseline	Measured in milimeters	After 6 hours of inhaled nitric oxide
Right Heart - RV fractional area change, change from baseline	Measured in percent	After 6 hours of inhaled nitric oxide
Right Heart - longitudinal myocardial velocity (S'), change from baseline	Measured in meters per second	After 6 hours of inhaled nitric oxide

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Heart Function	Left ventricular ejection fraction	After 6 hours of inhaled nitric oxide
Weaning success	Explore the effect of iNO on the rate of successful VA ECMO weaning.	Within 5 days of cannulation but may be repeated at 7 days if initially unsuccessful.
Long-term RV function	Assess RV function after LVAD implantation or cardiac transplantation if these occur during the same hospitalization.	Within three months of initial ECMO cannulation.

Collaborators and Investigators

• Sponsor: Filio Billia
• Collaborators: University of Toronto; Heart and Stroke Foundation of Canada; Peter Munk Cardiac Center
• Investigators: Principal Investigator: Filio Billia, MD PhD, University of Toronto, Peter Munk Cardiac Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2019
• Primary Completion (Anticipated): February 28, 2022
• Study Completion (Anticipated): February 28, 2022

Study Registration Dates

• First Submitted: September 16, 2019
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Right ventricle; Venoarterial ECMO; VA-ECMO weaning; Inhaled nitric oxide
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Shock; Myocardial Infarction; Infarction; Shock, Cardiogenic; 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: 15-8770

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes