Pulmonary Embolism
Conditions
Keywords
Pulmonary embolism clot
Brief summary
This is a randomized study to treat subjects diagnosed with pulmonary embolism with inhaled nitric oxide or placebo (oxygen).
Detailed description
This is a randomized, double blind study to treat subjects diagnosed with pulmonary embolism with inhaled nitrix oxide. In this clinical trial investigators will randomized patients to receive inhaled nitric oxide or sham (nitrogen + oxygen) for 24 hours. Patients must have a submassive pulmonary embolism (PE) and evidence of right ventricular (RV) heart dysfunction. Investigators hypothesize that the administration of inhaled NO + oxygen to patients with severe submassive PE will improve RV function, reduce RV strain and necrosis and improve dyspnea (difficulty breathing) more than sham oxygen treatment.
Interventions
DRUGInhaled Nitric Oxide
Nitric Oxide + oxygen
DRUGSham
Nitrogen + Oxygen
Sponsors
Mallinckrodt
National Institutes of Health (NIH)
University of Mississippi Medical Center
University of Texas, Southwestern Medical Center at Dallas
National Heart, Lung, and Blood Institute (NHLBI)
Indiana University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>/= 18 * Pulmonary imaging-proven PE, as interpreted by local radiologist * At least one predictor of RV dysfunction: 1. echocardiography with RV dilation or hypokinesis, 2. estimated RVSP \>40mm HG, 3. RV\>LV on CTPA, 4. elevated troponin I (\>0.1 ng/mL) or natriuretic peptide (BNP \> 90 pg/mL), 5. screening bedside cardiac ultrasound with color flow capability that shows RV dysfunction, 6. RV strain on ECG * Plan to admit to a bed with telemetry capability
Exclusion criteria
* Vasopressor support at time of enrollment * Pregnancy * Plan by clinical care team to use lytic or surgical embolectomy * Plan by clinical team to use platelet inhibiting drugs * Contraindication to anticoagulation * Altered mental status such that the patient is unable to provide informed consent * Inability to use a nasal cannula or face mask * Comfort care measures instituted * Supplemental oxygen requirements greater than can be administered via nasal cannula in order to maintain Sa)2 \> 80% * Pneumothorax with decompression * Serum MetHb \> 10% * Recent use of drugs known to increase cGMP * Use of nitroprusside or nitroglycerin within the last 4 hours * Use of any other nitrates with in the past 24 hours * Use of a fibrinolytic medicine within the past 14 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Normal Right Ventricular (RV) Function and Viability | 5 days or hospital discharge (whichever occurs first) | Right ventricular (RV) function and viability assessed by the composite of normal RV size (\<42 mm in diastole) and tricuspid annular plane systolic excursion (TAPSE) \> 16 mm and normal right ventricular index of myocardial performance (RIMP) \< 0.40 using spectral Doppler or \< 0.55 using tissue Doppler) and normal fractional area change (FAC) (\> 33%) and a serum hsTnT \< 14pg/mL. Missing values will be considered normal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Nitric Oxide Inhaled nitric oxide
Nitric Oxide + oxygen | 39 |
| Sham oxygen
Nitrogen + Oxygen | 39 |
| Total | 78 |
Baseline characteristics
| Characteristic | Inhaled Nitric Oxide | Sham | Total |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 15 | 59 years STANDARD_DEVIATION 16 | 57 years STANDARD_DEVIATION 15 |
| Region of Enrollment United States | 39 Participants | 39 Participants | 78 Participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Male | 18 Participants | 19 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 38 | 2 / 38 |
| other Total, other adverse events | 12 / 38 | 11 / 38 |
| serious Total, serious adverse events | 2 / 38 | 2 / 38 |
Outcome results
Primary
Number of Participants With Normal Right Ventricular (RV) Function and Viability
Right ventricular (RV) function and viability assessed by the composite of normal RV size (\<42 mm in diastole) and tricuspid annular plane systolic excursion (TAPSE) \> 16 mm and normal right ventricular index of myocardial performance (RIMP) \< 0.40 using spectral Doppler or \< 0.55 using tissue Doppler) and normal fractional area change (FAC) (\> 33%) and a serum hsTnT \< 14pg/mL. Missing values will be considered normal.
Time frame: 5 days or hospital discharge (whichever occurs first)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Nitric Oxide | Number of Participants With Normal Right Ventricular (RV) Function and Viability | 9 Participants |
| Sham | Number of Participants With Normal Right Ventricular (RV) Function and Viability | 5 Participants |