Clinical trial NCT04224103: Nitric Oxide in Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO)
Official title: Nitric Oxide in Right Ventricular Dysfunction: Improvements in Clinical and Hemodynamic Parameters on Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO; NOVICE)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Extracorporeal Membrane Oxygenation
Nitric Oxide
Shock, Cardiogenic
Keywords: Venoarterial ECMO
VA-ECMO weaning
Inhaled nitric oxide
Right ventricle
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Peter Munk Cardiac Center
name: Heart and Stroke Foundation of Canada
name: University of Toronto
First posted: 2020-01-13
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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).

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Participant recruitment
timeFrame: February 2020
measure: Right Heart - Qualitative function, change from baseline
timeFrame: After 6 hours of inhaled nitric oxide
measure: Right Heart - Tricuspid annular plane systolic excursion (TAPSE), change from baseline
timeFrame: After 6 hours of inhaled nitric oxide
measure: Right Heart - RV fractional area change, change from baseline
timeFrame: After 6 hours of inhaled nitric oxide
measure: Right Heart - longitudinal myocardial velocity (S'), change from baseline
timeFrame: After 6 hours of inhaled nitric oxide
Secondary outcomes:
measure: Left Heart Function
timeFrame: After 6 hours of inhaled nitric oxide
measure: Weaning success
timeFrame: Within 5 days of cannulation but may be repeated at 7 days if initially unsuccessful.
measure: Long-term RV function
timeFrame: Within three months of initial ECMO cannulation.
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University of Toronto, Peter Munk Cardiac Centre
name: Filio Billia, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: