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

Primary Purpose

Pulmonary Embolism

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

nitric oxide

About this trial

This is an interventional treatment trial for Pulmonary Embolism focused on measuring pulmonary hypertension, venous thromboembolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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)
SaO2% >80% at time of enrollment.
Patients must have a Borg score greater than 4/10.

Exclusion Criteria:

Altered mental status such that they are unable to provide consent.
Inability to use a nasal cannula or face mask (e.g., anatomic defect)
Supplemental oxygen requirement greater than can be administered via nasal cannula or face mask in order to maintain SaO2 >80%.
Pregnancy
Pneumothorax with decompression
A serum mtHb greater than 10%
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

Sites / Locations

Carolinas Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

iNO

Arm Description

gaseous NO is delivered by facemask

Outcomes

Primary Outcome Measures

Borg score

Secondary Outcome Measures

vital signs

Full Information

NCT ID

NCT00848731

First Posted

February 19, 2009

Last Updated

April 19, 2022

Sponsor

Wake Forest University Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT00848731

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2011

Overall Recruitment Status

Completed

Study Start Date

February 2009 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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 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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Embolism

Keywords

pulmonary hypertension, venous thromboembolism

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

iNO

Arm Type

Experimental

Arm Description

gaseous NO is delivered by facemask

Intervention Type

Drug

Intervention Name(s)

nitric oxide

Intervention Description

nitric oxide gas is delivered by facemask

Primary Outcome Measure Information:

Title

Borg score

Time Frame

3 hours

Secondary Outcome Measure Information:

Title

vital signs

Time Frame

3 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Inclusion Criteria: 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. 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) SaO2% >80% at time of enrollment. Patients must have a Borg score greater than 4/10. Exclusion Criteria: Altered mental status such that they are unable to provide consent. Inability to use a nasal cannula or face mask (e.g., anatomic defect) Supplemental oxygen requirement greater than can be administered via nasal cannula or face mask in order to maintain SaO2 >80%. Pregnancy Pneumothorax with decompression A serum mtHb greater than 10% Concurrent therapies including: Viagra® (sildenafil) use within the past 24 hours Levitra® (vardenafil) use within the past 24 hours Cialis® (tadalafil) use within the past 72 hours Use nitroprusside or nitroglycerine with in the past 4 hours Concomitant use of pressor or inotropic agents Use of fibrinolytic agent with in the past 14 days Use of nitrates within the past 24 hours

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeff A Kline, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Carolinas Medical Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28203

Country

United States

12. IPD Sharing Statement

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

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