Pulmonary EmbolismPhase 2NCT04996667
Effect of iNO in Patients With Submassive and Massive PE
A Phase 2 study testing inhaled nitric oxide (iNO) in people with Pulmonary Embolism and Pulmonary Embolism Subacute Massive, run by University of California, Los Angeles at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism, Pulmonary Embolism Subacute Massive
- What is being tested?
- inhaled nitric oxide (iNO)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2026to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
About this study
Official title: Study to Evaluate the Role of Inhaled Nitric Oxide (iNO) on Pulmonary Hemodynamics in Patients With Intermediate/Submassive and Massive Pulmonary Embolism (PE)
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).
Read the detailed description
This is a single center study to evaluate patients presenting with imaging confirmed intermediate/submassive or massive pulmonary embolism (PE). The investigators anticipate to enroll a total of 20-25 subjects at Ronald Reagan UCLA Medical Center.
After informed consent is obtained, the subject will proceed under one of two study intervention arms depending on his or her treatment plan. If the patient requires invasive treatment such as interventional thrombectomy or catheter-directed thrombolysis (CDT), the participant will be enrolled in the interventional radiology arm (invasive cohort). If the patient requires non-invasive treatment such as anticoagulation therapy, deep vein thrombosis (DVT) thrombectomy, or inferior vena cava (IVC) filter, the participant will be enrolled in the non-intervention arm (non-invasive cohort).
Interventional Radiology Arm (Invasive Cohort):
The following procedure will be performed:
Interventional radiology (IR) will perform a right heart catheterization (RHC) as part of a planned IR procedure. Patient arrives in the IR suite and is positioned flat with head of bed between flat and 45 degrees. O2 amount and modality, blood pressure, pressor name, dose, and rate will be recorded. If the patient is intubated, the sedation/analgesia drug name(s), dose(s), and rate(s) 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 (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.
Edwards ClearSight system and Edwards EV1000 clinical platform is a finger probe worn with a supportive forearm strap. Hemodynamic measurements from the finger cuff will be recorded at intervals.
Novel non-invasive methods of estimating stroke volume and associated cardiac output have the potential to revolutionize PE risk stratification and care. Non-invasive blood pressure (NIBP) monitors can even measure stroke volume beat to beat, allowing for continuous evaluation of cardiac function. NIBP systems are typically composed of a finger cuff with an inflatable bladder, pressure sensors, and light sensors. An arterial pulse contour is formed using the volume clamp method of blood pressure measurement combined with calibration and brachial pressure reconstruction algorithms. The stroke volume with each heart beat can be estimated as the area under the systolic portion of the blood pressure curve divided by the afterload. A limitation of using NIBP monitors to measure stroke volume is their relative inaccuracy, as they are calculations of an indirect measurement. However, NIBP monitors¬ may improve clinical care of PE because they allow for assessment of dynamic cardiac changes in real time. Detection of worsening stroke volume in acute PE could inform providers of impending cardiac collapse, and improvement of stroke volume may function as a positive prognostic factor or marker of therapeutic success. Use of NIBP monitors during acute PE to identify clinically significant changes in cardiac function may advance both PE prognostication and management.
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.
All major changes in pressures, sedation, vital signs, and major events will be recorded throughout the RHC procedure.
iNO is scheduled to be weaned off post RHC but the IR/anesthesia team may choose to keep the patient on iNO at their clinical discretion. The patient will then proceed to their standard of care IR procedures with planned intervention.
Non-intervention Arm (Non-invasive Cohort):
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.
If a subject initially enrolled in the Non-intervention Arm (Non-invasive Cohort) needs an invasive procedure, they will be removed from the study.
- Being tested
- inhaled nitric oxide (iNO)
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled nitric oxide (iNO)Drug
Also called INOmax
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: inhaled nitric oxide (iNO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
right atrial pressure (RAP)
right atrial pressure (RAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
right atrial pressure (RAP)
right atrial pressure (RAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
right atrial pressure (RAP)
right atrial pressure (RAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
right ventricular pressure (RVP)
right ventricular pressure (RVP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
right ventricular pressure (RVP)
right ventricular pressure (RVP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
right ventricular pressure (RVP)
right ventricular pressure (RVP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
pulmonary arterial pressure (PAP)
pulmonary arterial pressure (PAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
pulmonary arterial pressure (PAP)
pulmonary arterial pressure (PAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
pulmonary arterial pressure (PAP)
pulmonary arterial pressure (PAP) in mmHg
Measured: 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: 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: 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: 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: 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: 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: 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: 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: 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: measured invasively during a right heart catheterization (RHC) after administration of iNO
mixed venous O2
mixed venous O2 in %
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
mixed venous O2
mixed venous O2 in %
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
mixed venous O2
mixed venous O2 in %
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
central venous O2
central venous O2 in %
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
central venous O2
central venous O2 in %
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
central venous O2
central venous O2 in %
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
systemic PaO2
systemic PaO2 in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
systemic PaO2
systemic PaO2 in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
systemic PaO2
systemic PaO2 in mmHg
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
systolic blood pressure (SBP)
Systolic Blood Pressure in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
systolic blood pressure (SBP)
Systolic Blood Pressure in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
systolic blood pressure (SBP)
Systolic Blood Pressure in mmHg
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
diastolic blood pressure (DBP)
Diastolic Blood Pressure in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
diastolic blood pressure (DBP)
Diastolic Blood Pressure in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
diastolic blood pressure (DBP)
Diastolic Blood Pressure in mmHg
Measured: measured invasively during a right heart catheterization (RHC) after administration of iNO
mean arterial pressure (MAP)
mean arterial pressure (MAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) before administration of iNO
mean arterial pressure (MAP)
mean arterial pressure (MAP) in mmHg
Measured: measured invasively during a right heart catheterization (RHC) during administration of iNO
mean arterial pressure (MAP)
mean arterial pressure (MAP) in mmHg
Measured: 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: 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: 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: 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: 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: 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: 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: 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: 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: measured noninvasively after administration of inhaled nitric oxide (iNO)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start1 Jun 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Why it stopped: no sponsor support
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmbolismStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt
- Responsible party
- Principal investigator, Rajan Saggar, University of California, Los Angeles
- Investigators
- Rajan Saggar, M.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04996667
- Sponsor's protocol ID
- 21-000569
- Status last verified
- Mar 2026
- First submitted
- 21 Jul 2021
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22005573Capellier 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.
PubMed 9407246Szold 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.
PubMed 16598645Kline 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.
PubMed 30633959
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Role of Inhaled Nitric Oxide (iNO) on Pulmonary Hemodynamics in Patients With Intermediate/Submassive and Massive Pulmonary Embolism (PE)
- ClinicalTrials.gov ID
- NCT04996667
- Acronym / sponsor ID
- 21-000569
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no sponsor support
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Mallinckrodt
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 9 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a single center study to evaluate patients presenting with imaging confirmed intermediate/submassive or massive pulmonary embolism (PE). The investigators anticipate to enroll a total of 20-25 subjects at Ronald Reagan UCLA Medical Center.
After informed consent is obtained, the subject will proceed under one of two study intervention arms depending on his or her treatment plan. If the patient requires invasive treatment such as interventional thrombectomy or catheter-directed thrombolysis (CDT), the participant will be enrolled in the interventional radiology arm (invasive cohort). If the patient requires non-invasive treatment such as anticoagulation therapy, deep vein thrombosis (DVT) thrombectomy, or inferior vena cava (IVC) filter, the participant will be enrolled in the non-intervention arm (non-invasive cohort).
Interventional Radiology Arm (Invasive Cohort):
The following procedure will be performed:
Interventional radiology (IR) will perform a right heart catheterization (RHC) as part of a planned IR procedure. Patient arrives in the IR suite and is positioned flat with head of bed between flat and 45 degrees. O2 amount and modality, blood pressure, pressor name, dose, and rate will be recorded. If the patient is intubated, the sedation/analgesia drug name(s), dose(s), and rate(s) 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 (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.
Edwards ClearSight system and Edwards EV1000 clinical platform is a finger probe worn with a supportive forearm strap. Hemodynamic measurements from the finger cuff will be recorded at intervals.
Novel non-invasive methods of estimating stroke volume and associated cardiac output have the potential to revolutionize PE risk stratification and care. Non-invasive blood pressure (NIBP) monitors can even measure stroke volume beat to beat, allowing for continuous evaluation of cardiac function. NIBP systems are typically composed of a finger cuff with an inflatable bladder, pressure sensors, and light sensors. An arterial pulse contour is formed using the volume clamp method of blood pressure measurement combined with calibration and brachial pressure reconstruction algorithms. The stroke volume with each heart beat can be estimated as the area under the systolic portion of the blood pressure curve divided by the afterload. A limitation of using NIBP monitors to measure stroke volume is their relative inaccuracy, as they are calculations of an indirect measurement. However, NIBP monitors¬ may improve clinical care of PE because they allow for assessment of dynamic cardiac changes in real time. Detection of worsening stroke volume in acute PE could inform providers of impending cardiac collapse, and improvement of stroke volume may function as a positive prognostic factor or marker of therapeutic success. Use of NIBP monitors during acute PE to identify clinically significant changes in cardiac function may advance both PE prognostication and management.
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.
All major changes in pressures, sedation, vital signs, and major events will be recorded throughout the RHC procedure.
iNO is scheduled to be weaned off post RHC but the IR/anesthesia team may choose to keep the patient on iNO at their clinical discretion. The patient will then proceed to their standard of care IR procedures with planned intervention.
Non-intervention Arm (Non-invasive Cohort):
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.
If a subject initially enrolled in the Non-intervention Arm (Non-invasive Cohort) needs an invasive procedure, they will be removed from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interventional Radiology Arm (Invasive Cohort) | Active comparator | Drug: inhaled nitric oxide (iNO)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. |
| Non-intervention Arm (Non-invasive Cohort) | Active comparator | Drug: inhaled nitric oxide (iNO)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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):
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inhaled nitric oxide (iNO)Also: INOmaxInhaled 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. | Drug | Interventional Radiology Arm (Invasive Cohort), Non-intervention Arm (Non-invasive Cohort) |
Primary outcome
right atrial pressure (RAP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
right atrial pressure (RAP) in mmHg
right atrial pressure (RAP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
right atrial pressure (RAP) in mmHg
right atrial pressure (RAP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
right atrial pressure (RAP) in mmHg
right ventricular pressure (RVP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
right ventricular pressure (RVP) in mmHg
right ventricular pressure (RVP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
right ventricular pressure (RVP) in mmHg
right ventricular pressure (RVP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
right ventricular pressure (RVP) in mmHg
pulmonary arterial pressure (PAP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
pulmonary arterial pressure (PAP) in mmHg
pulmonary arterial pressure (PAP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
pulmonary arterial pressure (PAP) in mmHg
pulmonary arterial pressure (PAP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
pulmonary arterial pressure (PAP) in mmHg
pulmonary capillary wedge pressure (PCWP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
pulmonary capillary wedge pressure (PCWP) in mmHg
pulmonary capillary wedge pressure (PCWP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
pulmonary capillary wedge pressure (PCWP) in mmHg
pulmonary capillary wedge pressure (PCWP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
pulmonary capillary wedge pressure (PCWP) in mmHg
cardiac output (CO) (by Fick and Thermodilution)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
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).
cardiac output (CO) (by Fick and Thermodilution)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
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).
cardiac output (CO) (by Fick and Thermodilution)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
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).
cardiac index (CI) (by Fick and Thermodilution)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
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).
cardiac index (CI) (by Fick and Thermodilution)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
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).
cardiac index (CI) (by Fick and Thermodilution)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
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).
mixed venous O2
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
mixed venous O2 in %
mixed venous O2
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
mixed venous O2 in %
mixed venous O2
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
mixed venous O2 in %
central venous O2
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
central venous O2 in %
central venous O2
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
central venous O2 in %
central venous O2
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
central venous O2 in %
systemic PaO2
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
systemic PaO2 in mmHg
systemic PaO2
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
systemic PaO2 in mmHg
systemic PaO2
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
systemic PaO2 in mmHg
systolic blood pressure (SBP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
Systolic Blood Pressure in mmHg
systolic blood pressure (SBP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
Systolic Blood Pressure in mmHg
systolic blood pressure (SBP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
Systolic Blood Pressure in mmHg
diastolic blood pressure (DBP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
Diastolic Blood Pressure in mmHg
diastolic blood pressure (DBP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
Diastolic Blood Pressure in mmHg
diastolic blood pressure (DBP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
Diastolic Blood Pressure in mmHg
mean arterial pressure (MAP)
Time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO
mean arterial pressure (MAP) in mmHg
mean arterial pressure (MAP)
Time frame: measured invasively during a right heart catheterization (RHC) during administration of iNO
mean arterial pressure (MAP) in mmHg
mean arterial pressure (MAP)
Time frame: measured invasively during a right heart catheterization (RHC) after administration of iNO
mean arterial pressure (MAP) in mmHg
blood pressure (BP) (measured noninvasively)
Time frame: measured noninvasively before administration of inhaled nitric oxide (iNO)
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
blood pressure (BP) (measured noninvasively)
Time frame: measured noninvasively during administration of inhaled nitric oxide (iNO)
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
blood pressure (BP) (measured noninvasively)
Time frame: measured noninvasively after administration of inhaled nitric oxide (iNO)
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
heart rate (HR) (measured noninvasively)
Time frame: measured noninvasively before administration of inhaled nitric oxide (iNO)
The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM)
heart rate (HR) (measured noninvasively)
Time frame: measured noninvasively during administration of inhaled nitric oxide (iNO)
The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM)
heart rate (HR) (measured noninvasively)
Time frame: measured noninvasively after administration of inhaled nitric oxide (iNO)
The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM)
cardiac index (CI) (measured noninvasively)
Time frame: measured noninvasively before administration of inhaled nitric oxide (iNO)
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).
cardiac index (CI) (measured noninvasively)
Time frame: measured noninvasively during administration of inhaled nitric oxide (iNO)
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).
cardiac index (CI) (measured noninvasively)
Time frame: measured noninvasively after administration of inhaled nitric oxide (iNO)
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).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Results publication: PubMed 22005573Summerfield 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.
- Results publication: PubMed 9407246Capellier 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.
- Results publication: PubMed 16598645Szold 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.
- Results publication: PubMed 30633959Kline 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.
- Edwards ClearSight systemLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Pulmonary Embolism
RecruitingObservational study
Study of the Long-Term Safety and Outcomes of Treating Pulmonary Embolism With the Indigo Aspiration System
Pulmonary Embolism
Not yet recruiting
Pilot Study Evaluating Catheter Directed Thrombolysis Device in Acute Intermediate Risk Pulmonary Embolism
Pulmonary Embolism (PE), Pulmonary Embolism With Right Ventricle Enlargement
RecruitingObservational study
Inari VISION Registry
Pulmonary Embolism
RecruitingPhase 3
Treatment and Secondary Prevention of Venous Thromboembolism (VTE) in Adult Participants With Solid and Hematologic Cancers
Venous Thromboembolism (VTE)
RecruitingPhase 3
REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis
Cancer-Associated Thrombosis (CAT)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajan Saggar, M.D. principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing inhaled nitric oxide (iNO) in people with Pulmonary Embolism and Pulmonary Embolism Subacute Massive, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
right atrial pressure (RAP) (time frame: measured invasively during a right heart catheterization (RHC) before administration of iNO). The study lists 45 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04996667, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.