Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Nitric Oxide to Treat Pulmonary Embolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Indiana University
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)
Information provided by (Responsible Party):
Jeffrey Kline, Indiana University Identifier:
First received: August 28, 2013
Last updated: March 9, 2016
Last verified: March 2016
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.

Condition Intervention Phase
Pulmonary Embolism
Drug: Nitric Oxide + oxygen
Drug: Nitrogen + Oxygen
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism

Resource links provided by NLM:

Further study details as provided by Indiana University:

Primary Outcome Measures:
  • RV function and viability [ Time Frame: 5 days or hospital discharge (whichever occurs first) ] [ Designated as safety issue: No ]
    RV function and viability assessed by the composite of normal RV size (<42 mm in diastole) and TAPSE > 16 mm and normal RIMP < 0.40 using spectral Doppler or < 0.55 using tissue Doppler) and normal FAC (> 33%) and a serum hsTnT < 14pg/mL. Missing values will be considered normal.

Estimated Enrollment: 78
Study Start Date: October 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inhaled Nitric Oxide
Inhaled nitric oxide
Drug: Nitric Oxide + oxygen
Sham Comparator: Sham
Drug: Nitrogen + Oxygen


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01939301

Contact: Jeffrey A Kline, MD 317-880-3869
Contact: Cassandra L Hall, CCRC 317-962-1190

United States, Indiana
Eskenazi Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Jeffrey A Kline, MD         
Indiana University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Jeffrey A Kline, MD         
Methodist Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Jeff A Kline, MD         
United States, Mississippi
University of Mississippi Recruiting
Jackson, Mississippi, United States, 36216
Principal Investigator: Alan Jones, MD         
United States, Texas
UT Southwestern Medical Center Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Emily Gundert, MD    214-648-3916   
Contact: Khushbakht Bakhshi    214-648-9982   
Sponsors and Collaborators
Indiana University School of Medicine
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)
Principal Investigator: Jeff A Kline, MD Indiana University
  More Information

Responsible Party: Jeffrey Kline, Vice Chair of Research, Indiana University Identifier: NCT01939301     History of Changes
Other Study ID Numbers: Kline-1UM NO for PE  1UM1HL113203-01A1 
Study First Received: August 28, 2013
Last Updated: March 9, 2016
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Indiana University:
Pulmonary embolism clot

Additional relevant MeSH terms:
Embolism and Thrombosis
Pulmonary Embolism
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents processed this record on January 17, 2017