Effect of iNO in Patients With Submassive and Massive PE

NCT04996667 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 21-000569
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

A single center study to evaluate the effect of inhaled nitric oxide (iNO) on pulmonary dynamics in patients presenting with imaging confirmed intermediate/submassive or massive pulmonary embolism (PE). The target enrollment is 20 subjects at Ronald Reagan UCLA Medical Center. PE patients undergoing catheter-based intervention will be administered iNO during their intervention and pulmonary hemodynamic measurement will be measured before, during, and after iNO administration (Invasive Cohort). Patients who are not undergoing catheter-based intervention will also be administered iNO and will have pulmonary hemodynamics, blood pressure, and heart rate measured non-invasively (Non-Invasive Cohort).

Conditions

Pulmonary Embolism; Pulmonary Embolism Subacute Massive

Outcome Measures

Primary Outcomes (45)

• right atrial pressure (RAP)

  right atrial pressure (RAP) in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• right atrial pressure (RAP)

  right atrial pressure (RAP) in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• right atrial pressure (RAP)

  right atrial pressure (RAP) in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• right ventricular pressure (RVP)

  right ventricular pressure (RVP) in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• right ventricular pressure (RVP)

  right ventricular pressure (RVP) in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• right ventricular pressure (RVP)

  right ventricular pressure (RVP) in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• pulmonary arterial pressure (PAP)

  pulmonary arterial pressure (PAP) in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• pulmonary arterial pressure (PAP)

  pulmonary arterial pressure (PAP) in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• pulmonary arterial pressure (PAP)

  pulmonary arterial pressure (PAP) in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• pulmonary capillary wedge pressure (PCWP)

  pulmonary capillary wedge pressure (PCWP) in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• pulmonary capillary wedge pressure (PCWP)

  pulmonary capillary wedge pressure (PCWP) in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• pulmonary capillary wedge pressure (PCWP)

  pulmonary capillary wedge pressure (PCWP) in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• cardiac output (CO) (by Fick and Thermodilution)

  Cardiac Output (CO) is the amount of blood the heart pumps from each ventricle per minute. It is usually expressed in litres per minute (L/min).

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• cardiac output (CO) (by Fick and Thermodilution)

  Cardiac Output (CO) is the amount of blood the heart pumps from each ventricle per minute. It is usually expressed in litres per minute (L/min).

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• cardiac output (CO) (by Fick and Thermodilution)

  Cardiac Output (CO) is the amount of blood the heart pumps from each ventricle per minute. It is usually expressed in litres per minute (L/min).

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• cardiac index (CI) (by Fick and Thermodilution)

  Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• cardiac index (CI) (by Fick and Thermodilution)

  Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• cardiac index (CI) (by Fick and Thermodilution)

  Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• mixed venous O2

  mixed venous O2 in %

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• mixed venous O2

  mixed venous O2 in %

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• mixed venous O2

  mixed venous O2 in %

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• central venous O2

  central venous O2 in %

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• central venous O2

  central venous O2 in %

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• central venous O2

  central venous O2 in %

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• systemic PaO2

  systemic PaO2 in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• systemic PaO2

  systemic PaO2 in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• systemic PaO2

  systemic PaO2 in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• systolic blood pressure (SBP)

  Systolic Blood Pressure in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• systolic blood pressure (SBP)

  Systolic Blood Pressure in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• systolic blood pressure (SBP)

  Systolic Blood Pressure in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• diastolic blood pressure (DBP)

  Diastolic Blood Pressure in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• diastolic blood pressure (DBP)

  Diastolic Blood Pressure in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• diastolic blood pressure (DBP)

  Diastolic Blood Pressure in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• mean arterial pressure (MAP)

  mean arterial pressure (MAP) in mmHg

  measured invasively during a right heart catheterization (RHC) before administration of iNO

• mean arterial pressure (MAP)

  mean arterial pressure (MAP) in mmHg

  measured invasively during a right heart catheterization (RHC) during administration of iNO

• mean arterial pressure (MAP)

  mean arterial pressure (MAP) in mmHg

  measured invasively during a right heart catheterization (RHC) after administration of iNO

• blood pressure (BP) (measured noninvasively)

  The pressure of the blood in the circulatory system, often measured for diagnosis since it is closely related to the force and rate of the heartbeat and the diameter and elasticity of the arterial walls. Systolic Blood Pressure in mmHg Diastolic Blood Pressure in mmHg

  measured noninvasively before administration of inhaled nitric oxide (iNO)

• blood pressure (BP) (measured noninvasively)

  The pressure of the blood in the circulatory system, often measured for diagnosis since it is closely related to the force and rate of the heartbeat and the diameter and elasticity of the arterial walls. Systolic Blood Pressure in mmHg Diastolic Blood Pressure in mmHg

  measured noninvasively during administration of inhaled nitric oxide (iNO)

• blood pressure (BP) (measured noninvasively)

  The pressure of the blood in the circulatory system, often measured for diagnosis since it is closely related to the force and rate of the heartbeat and the diameter and elasticity of the arterial walls. Systolic Blood Pressure in mmHg Diastolic Blood Pressure in mmHg

  measured noninvasively after administration of inhaled nitric oxide (iNO)

• heart rate (HR) (measured noninvasively)

  The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM)

  measured noninvasively before administration of inhaled nitric oxide (iNO)

• heart rate (HR) (measured noninvasively)

  The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM)

  measured noninvasively during administration of inhaled nitric oxide (iNO)

• heart rate (HR) (measured noninvasively)

  The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM)

  measured noninvasively after administration of inhaled nitric oxide (iNO)

• cardiac index (CI) (measured noninvasively)

  Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).

  measured noninvasively before administration of inhaled nitric oxide (iNO)

• cardiac index (CI) (measured noninvasively)

  Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).

  measured noninvasively during administration of inhaled nitric oxide (iNO)

• cardiac index (CI) (measured noninvasively)

  Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).

  measured noninvasively after administration of inhaled nitric oxide (iNO)

Study Arms (2)

Interventional Radiology Arm (Invasive Cohort)

ACTIVE COMPARATOR

Interventional radiology (IR) will perform a right heart catheterization (RHC) as part of a planned IR procedure. Bedside apical 4 chamber view (RV:LV ratio) will be recorded using an ultrasound device, and noninvasive RV data will be obtained with Edwards ClearSight system and Edwards EV1000 clinical platform. The Butterfly iQ+ (one possible ultrasound device which may be used) is a single-probe, whole-body ultrasound device. After initial measurements, inhaled nitric oxide (iNO) will be administered at 30 ppm for 3 minutes. The same measurements will be obtained/calculated before, during iNO administration, and after iNO has been withheld for 2 minutes.

Drug: inhaled nitric oxide (iNO)

Non-intervention Arm (Non-invasive Cohort)

ACTIVE COMPARATOR

Vitals including O2 amount and modality, blood pressure, pressor name, dose, and rate will be recorded. If the patient is intubated, the name, dose, and rate of sedation and analgesia will be recorded. If the patient is not intubated, name and dose amount of sedation will be recorded. Arterial blood gas will be obtained if an A-line is placed. Bedside apical 4 chamber view will be recorded (RV:LV ratio) with an ultrasound device, and noninvasive RV data will be obtained with Edwards ClearSight system and Edwards EV1000 clinical platform. This data will be obtained before, during iNO administration, and after iNO has been withheld for 2 minutes.

Drug: inhaled nitric oxide (iNO)

Interventions

inhaled nitric oxide (iNO) DRUG

Inhaled nitric oxide (iNO), which is known mainly from the pulmonary hypertension literature for its therapeutic role in pulmonary arterial hypertension, has been proposed as a potential pharmacologic adjunct to standard anticoagulation in acute PE. Inhaled nitric oxide (iNO) will be administered at 30 ppm for 3 minutes. The measurements will be obtained/calculated before, during iNO administration, and after iNO has been withheld for 2 minutes.

Also known as: INOmax

Interventional Radiology Arm (Invasive Cohort); Non-intervention Arm (Non-invasive Cohort)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient ≥ 18 years of age.
• The patient or patient's surrogate decision maker must understand and sign the informed consent form (ICF).
• Hospitalized (Emergency Room (ER) or inpatient) with:
• Imaging (computed tomography pulmonary angiography (CTPA) or ventilation/perfusion (VQ) lung scan) proven acute pulmonary embolism (PE)
• PE meets the following intermediate risk PE criteria (or massive, see below):
• Troponin \> .1 AND
• Imaging (computed tomography (CT) or transthoracic echocardiogram (TTE)) signs of RV compromise (at least 1 of the following):
• RV:LV\>1 on TTE or CTPA OR RV dilation (TTE or CTPA OR RV dysfunction on TTE.
• Massive PE
• Intensive care unit (ICU) level of care (Patient moving to ICU, ICU level of care in ER, or currently in ICU)
• Ability to comply with study protocol in investigator's judgement

You may not qualify if:

• Pregnancy or breastfeeding
• Inability to administer iNO through current mode of O2 delivery (i.e. BiPAP)
• Active hemoptysis
• Known allergy to iNO.
• Any serious medical condition of lab abnormality that, in the investigator's judgement, precludes the patient's safe participation in the study.
• Methemoglobin reductase deficiency
• Unable to obtain consent or patient or patient surrogate decision maker declines
• Patients already on iNO prior to study enrollment

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Mallinckrodt: collaborator

Study Sites (1)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Related Publications (4)

• Summerfield DT, Desai H, Levitov A, Grooms DA, Marik PE. Inhaled nitric oxide as salvage therapy in massive pulmonary embolism: a case series. Respir Care. 2012 Mar;57(3):444-8. doi: 10.4187/respcare.01373. Epub 2011 Oct 12.

  PMID: 22005573 RESULT

• Capellier G, Jacques T, Balvay P, Blasco G, Belle E, Barale F. Inhaled nitric oxide in patients with pulmonary embolism. Intensive Care Med. 1997 Oct;23(10):1089-92. doi: 10.1007/s001340050461.

  PMID: 9407246 RESULT

• Szold O, Khoury W, Biderman P, Klausner JM, Halpern P, Weinbroum AA. Inhaled nitric oxide improves pulmonary functions following massive pulmonary embolism: a report of four patients and review of the literature. Lung. 2006 Jan-Feb;184(1):1-5. doi: 10.1007/s00408-005-2550-7.

  PMID: 16598645 RESULT

• Kline JA, Puskarich MA, Jones AE, Mastouri RA, Hall CL, Perkins A, Gundert EE, Lahm T. Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial. Nitric Oxide. 2019 Mar 1;84:60-68. doi: 10.1016/j.niox.2019.01.006. Epub 2019 Jan 8.

  PMID: 30633959 RESULT

Related Links

• Edwards ClearSight system

MeSH Terms

Conditions

Pulmonary Embolism

Interventions

Endothelium-Dependent Relaxing Factors

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Rajan Saggar, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 9, 2021
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)