Phase I Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism
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.
- 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.
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.
- 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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism|
- Borg score [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]
- vital signs [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
gaseous NO is delivered by facemask
Drug: nitric oxide
nitric oxide gas is delivered by facemask
We propose to enroll a total of 25 patients with recently diagnosed pulmonary embolism. Inclusion criteria will include moderate to severe shortness of breath as rated by the patient on a standard scoring system, a systolic blood pressure of >89 mm Hg unless the patient has a known prior history of low blood pressure, and blood oxygen saturation of >80%. Exclusion criteria will include: altered mental status, inability to use a nasal cannula, a large need for supplemental oxygen, pregnancy, pneumothorax, recent use of nitrate-containing medications, recent use of thrombolytic drugs, requirement for inotropic or pressor support, or a level of methemoglobin greater than 10%.
After obtaining informed consent, subjects will have blood drawn and vital signs will be obtained. They will subsequently begin to breathe oxygen and NO supplied through a nasal cannula delivered from the iNOvent device. The patients will undergo serial measurements of their blood pressure, arterial oxygen saturation and will have their serum methemoglobin level monitored via a non-invasive probe. Titration of the amount of NO delivered will be made periodically based on the patient's vital signs. If an absolute safety endpoint is reached, NO will be rapidly weaned. Based on the patient's response to NO as determined by their vital signs, a maintenance dose of NO, not to exceed 25 ppm, will be reached. Subjects will continue to receive this concentration for up to 2 hours prior to weaning. Patients will be asked once more to rate the severity of their shortness of breath and blood will be drawn just prior to weaning. Should the patient reach a safety endpoint, the NO will be weaned at an earlier timepoint.
We will determine the percentage of patients able to complete the full protocol without reaching a safety endpoint, the percent change in methemoglobin level, the trend in patient-reported shortness of breath, percent change in SBP and oxygen saturation and the number of patients who withdraw during induction for any reason.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00848731
|United States, North Carolina|
|Carolinas Medical Center|
|Charlotte, North Carolina, United States, 28203|