Iloprost Effects on Gas Exchange and Pulmonary Mechanics

This study has been completed.
Sponsor:
Collaborator:
Actelion
Information provided by (Responsible Party):
Gary Kinasewitz, University of Oklahoma
ClinicalTrials.gov Identifier:
NCT01274481
First received: November 15, 2010
Last updated: August 8, 2012
Last verified: August 2012
  Purpose

This study will examine the hypothesis that iloprost maintains and improves ventilation perfusion matching in patients with pulmonary hypertension and ARDS/ALI as reflected by 1) an improved PaO2/FIO2 ratio as calculated from the measured arterial blood gases obtained before and after iloprost administration, 2) an improvement in lung compliance, and 3) an improvement in the ventilatory equivalents for oxygen and CO2 measured by expired gas analysis.


Condition Intervention Phase
Acute Respiratory Distress Syndrome
Acute Lung Injury
Pulmonary Hypertension
Drug: Iloprost
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Iloprost on Gas Exchange and Pulmonary Mechanics in Patients With Pulmonary Hypertension and ARDS/ALI

Resource links provided by NLM:


Further study details as provided by University of Oklahoma:

Primary Outcome Measures:
  • Arterial oxygenation [ Time Frame: 30 minutes ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Lung compliance [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: March 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Iloprost
All patients will have their response to Iloprost compared to baseline pre-treatment.
Drug: Iloprost
patients inhale 20 mcg of Iloprost via nebulizer and, if oxygenation and blood pressure is maintained receive a second dose of 20 mcg of Iloprost 30 minutes later.
Other Name: Ventavis

Detailed Description:

Purpose/hypothesis This study will examine the hypothesis that iloprost maintains and improves ventilation perfusion matching in patients with pulmonary hypertension and ARDS/ALI as reflected by 1) an improved PaO2/FIO2 ratio as calculated from the measured arterial blood gases obtained before and after iloprost administration, 2) an improvement in lung compliance, and 3) an improvement in the ventilatory equivalents for oxygen and CO2 measured by expired gas analysis.

Experimental design Twenty patients with pulmonary hypertension and ARDS/ALI will be enrolled. This will be 2-3 hour study conducted on a single day in which each patient's baseline measurements obtained prior to iloprost administration are compared to measurements obtained 30 minutes and 2 hours after Iloprost inhalation. While critically ill by virtue of their underlying illness, patients will be clinically stable over the preceding 2 hours prior to entry into the study as evidenced by airway pressures and arterial O2 saturation that vary less than 10% on the same ventilator settings.

Proposed procedure After baseline measurements are obtained, 10 mcg iloprost will be administered via nebulizer on the inspiratory line of the ventilator. Vital signs including blood pressure and heart rate, respiratory rate and arterial saturation by pulse oximetry will be monitored at baseline and q 5 minutes after the inhalation of iloprost. Thirty (30) minutes after the administration of iloprost the gas exchange, pulmonary function and arterial blood gas measurements will be repeated as described above. Patients who remain clinically stable as evidenced by a fall in arterial PO2 <5 mm Hg, fall in systemic blood pressure of <10% and increase in heart rate of <10 beats/min as well as the absence of symptoms 30 minutes after the inhalation of 20 mcg of iloprost will receive a second dose of 20 mcg. Vital signs will continue to be monitored continuously and 30 minutes after the second dose of iloprost, all pulmonary measurements will be repeated. All patients will be monitored continuously for at least 2 hours after the final dose of iloprost and pulmonary testing will be repeated for a final time 2 hours after the last administration of iloprost. Patients will be deemed to have completed the study after 2 hours provided their vital signs have returned to within 10% of baseline values.

Importance of knowledge reasonably expected to result from the research A positive result in this pilot study will provide a strong rationale leading to a larger long-term study examining the effect of continuous iloprost therapy over several days on pulmonary hemodynamics, gas exchange, and outcome in patients with ARDS/ALI. Markers of inflammation (IL-6 and IL-8), coagulation (thrombin-antithrombin complexes and D-dimer) and collagen formation (TGF* and procollagen peptide III) in lung BAL fluid would be monitored to demonstrate iloprost's potential beneficial effects on lung remodeling in this devastating disorder.

If the research involves more than minimal risk, describe the research plan for monitoring the data collected to ensure the safety of participants.

Data safety monitoring board will meet after the first six patients and determine whether to continue.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Pulmonary hypertension as evidenced by:

    • In patients with a pulmonary artery catheter, a mean pulmonary arterial pressure greater then 25 mmHg with a pulmonary capillary wedge pressure less than or equal to 15 mmHg, or
    • Echocardiographic evidence of pulmonary arterial hypertension including

      • a PA systolic pressure greater than 35 mmHg, or
      • in those patients in whom a PA systolic cannot be estimated for technical reasons, RV dilatation and/or decreased RV function in the presence of normal LV function.
  2. ARDS/ALI as indicated by:

    • Diffuse pulmonary infiltrates involving at least three of four quadrants on chest x-ray.
    • PaO2/FIO2 less than 300 while on mechanical ventilation.
    • Recognized cause of ARDS/ALI
    • Absence of clinical evidence of left atrial hypertension
  3. presence of an arterial line for pressure monitoring and blood sampling, and
  4. the ability to obtain informed consent from the patient or next of kin.

Exclusion Criteria:

  1. clinical instability as evidenced by changes in ventilator settings or medications within the preceding hour, and
  2. presence of left ventricular dysfunction and/or left atrial enlargement by cardiac echo, or catheterization,
  3. Liver failure (Child-Pugh Class B or C)
  4. Renal failure on dialysis
  5. Pregnancy: all females of child-bearing potential will have a negative pregnancy test before being allowed to enroll
  6. Systolic blood pressure less than 85 mm Hg or the need for pressors in the first 10 patients; after review of the first 10 patients by the DMSB, patients on norepinephrine (without additional pressors) in doses less than 0.2 mcg/kg/min may be enrolled if the DMSB finds no evidence of iloprost induced systemic hypotension in the first 10 patients
  7. Thrombocytopenia, bleeding diathesis or active bleeding
  8. Asthma/Severe bronchospasm
  9. Age < 18 years
  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 ClinicalTrials.gov identifier: NCT01274481

Locations
United States, Oklahoma
OU Medical Center
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
University of Oklahoma
Actelion
Investigators
Principal Investigator: Gary Kinasewitz, MD University of Oklahoma
  More Information

No publications provided by University of Oklahoma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gary Kinasewitz, Principal Investigator, University of Oklahoma
ClinicalTrials.gov Identifier: NCT01274481     History of Changes
Other Study ID Numbers: 15123
Study First Received: November 15, 2010
Last Updated: August 8, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Oklahoma:
Acute Respiratory Distress Syndrome
Acute Lung Injury
pulmonary hypertension
oxygenation
lung mechanics
gas exchange

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Wounds and Injuries
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
Iloprost
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 24, 2014