Phase I Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism
Information source: Carolinas Healthcare System
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pulmonary Embolism
Intervention: nitric oxide (Drug)
Phase: Phase 1
Sponsored by: Carolinas Healthcare System
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.
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.
Official title: Phase I Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism
Study design: Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Primary outcome: Borg score
Secondary outcome: vital signs
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.
Minimum age: 18 Years.
Maximum age: N/A.
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.
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%.
5. Pneumothorax with decompression
6. A serum mtHb greater than 10%
7. Concurrent therapies including:
1. ViagraÂ® (sildenafil) use within the past 24 hours
2. LevitraÂ® (vardenafil) use within the past 24 hours
3. CialisÂ® (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
Locations and Contacts
Carolinas Medical Center, Charlotte, North Carolina 28203, United States; Recruiting
Jeffrey A Kline, MD, Phone: 704-355-7092, Email: email@example.com
Alan E Jones, MD, Sub-Investigator
Michael R Marchick, MD, Sub-Investigator
John S Garrett, MD, Sub-Investigator
William Tsia, MD, Sub-Investigator
Starting date: February 2009
Last updated: February 19, 2009