Phase I Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism

• Status: Completed
• Trial end date: 2011-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will test the hypothesis that patients with acute PE and dyspnea can safely inhale NO. The secondary hypothesis is that patients who are blinded to the inhaled NO concentration will sustain subjective improvement in their perception of dyspnea based upon their reported Borg dyspnea score, during inhalation of NO.

Specific aims

1. Test if patients with acute PE and shortness of breath of severity ≥ 5 on a 0-10 scale called the Borg score can have inhaled nitric oxide administered via nasal cannula or face mask in a titration protocol that increases concentration by 5 ppm in 5 min steps to a maximum of 25 ppm.

2. We will measure the number of patients who meet an absolute safety endpoint during titration. An absolute safety endpoint requires execution of a rapid weaning protocol (2 ppm decrease per minute to 0 ppm).

Absolute safety endpoints: Two consecutive SBP measurements more than one min apart with both readings < 80 mm Hg;SaO 2 <80% for more than 15 seconds; Patient deterioration as defined by: Clinical decision for need of inotropic or pressor support for any reason, seizure, new altered mental status, focal neurological signs suggestive of cerebral ischemia, evidence of myocardial ischemia, protracted vomiting.

3. Test if the patient-reported Borg score decreases with administration of NO. Patients will not be told any details about the timing of the titration and will not be made aware of their iNO concentration when the Borg score is assessed.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Atrium Health; Carolinas Healthcare System
• Treatments: Nitric Oxide

Criteria

Inclusion Criteria:

Inclusion Criteria:

1. Diagnosis of acute PE requires symptoms of PE present <14 days with CT angiography interpreted as positive for acute PE. Initial evaluation for PE must be predicated upon the investigation of new or unexplained cardiopulmonary or chest-related clinical features consistent with PE, including shortness of breath, chest pain, respiratory distress, dizziness, unexplained tachypnea, tachycardia, syncope, cough or hemoptysis. All patients must have CT chest angiography with <2 mm collimation,(36) with or without indirect venography. Pulmonary arterial opacification will be achieved with power injection of non-ionic, low osmolar contrast in an antecubital vein with a timing run; the pitch, voltage, gantry speed and other technical details appropriate for each scanner.(37;38) Images will be interpreted as positive for intrapulmonary arterial filling defect consistent with acute PE using our published definitions(37;38) by a board-certified radiologist with specialty training in body CT or emergency medicine imaging in all cases.

2. SBP (SBP)> 89 mm Hg at the time of enrollment. We will allow enrollment for a patient with an SBP < 90 mm Hg prior to enrollment, or a patient with a SBP>80 mm Hg, if the patient has a documented or patient-identified history of low blood pressure and has no symptoms of shock, as described by Jones et al.(39)

3. SaO2% >80% at time of enrollment.

4. Patients must have a Borg score greater than 4/10.

Exclusion Criteria:

1. Altered mental status such that they are unable to provide consent.

2. Inability to use a nasal cannula or face mask (e.g., anatomic defect)

3. Supplemental oxygen requirement greater than can be administered via nasal cannula or face mask in order to maintain SaO2 >80%.

4. Pregnancy

5. Pneumothorax with decompression

6. A serum mtHb greater than 10%

7. Concurrent therapies including:

1. Viagra® (sildenafil) use within the past 24 hours

2. Levitra® (vardenafil) use within the past 24 hours

3. Cialis® (tadalafil) use within the past 72 hours

4. Use nitroprusside or nitroglycerine with in the past 4 hours

5. Concomitant use of pressor or inotropic agents

6. Use of fibrinolytic agent with in the past 14 days

7. Use of nitrates within the past 24 hours