EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)
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| ClinicalTrials.gov Identifier: NCT01681225 |
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Recruitment Status :
Completed
First Posted : September 7, 2012
Last Update Posted : December 3, 2019
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Sponsor:
Beth Israel Deaconess Medical Center
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Daniel Talmor, Beth Israel Deaconess Medical Center
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Brief Summary:
This phase II multi-centered, randomized controlled trial of mechanical ventilation directed by esophageal pressure measurement will test the primary hypothesis that using a strategy of maintaining a minimal but positive transpulmonary pressure (Ptp = airway pressure minus pleural pressure) throughout the ventilatory cycle will lead to an improvement in patient survival.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Respiratory Distress Syndrome | Other: Esophageal-pressure guided mechanical ventilation Other: High PEEP mechanical ventilation | Not Applicable |
This phase II prospective randomized controlled trial of ventilation directed by esophageal pressure measurements will enroll 200 patients with moderate to severe ARDS by the Berlin conference definition in several academic medical centers in North America. The control group will be ventilated using an alternative high-PEEP strategy with PEEP and FiO2 set using to an empiric table.
Plasma samples will be obtained at enrollment and days 3 and 7 and assessed for a variety of lung injury biomarkers to better assess the association between our intervention and the inflammation associated with mechanical ventilation and the development of ARDS. Hospital survivors will undergo a brief follow up phone survey to assess survival, functional status (Barthel Index), health-related QOL (Short Form 12), and frailty (VES) twelve months after enrollment.
The study length will be six years with a six month start-up period followed by a planned 50 month enrollment and twelve month follow-up.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 202 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2) |
| Actual Study Start Date : | October 31, 2012 |
| Actual Primary Completion Date : | October 12, 2017 |
| Actual Study Completion Date : | October 19, 2018 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: EPVent
The overall goals for the "EPVent" group (esophageal-pressure guided mechanical ventilation) are to employ an open-lung strategy that includes low tidal volumes and maintenance of a positive transpulmonary pressure at end-expiration [Ptpexp]. Fraction of inspired oxygen [FiO2] and transpulmonary pressure pressure during an expiratory hold will be changed to achieve values shown in one of the columns of a protocol-specified table to meet the oxygenation target.
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Other: Esophageal-pressure guided mechanical ventilation
Other Names:
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Active Comparator: Control
The overall goals for the Control group are similar to those for the EPVent group: to employ an open-lung strategy that includes low tidal volumes using an alternative high positive end-expiratory pressure [PEEP] strategy. The control group PEEP and tidal volume will be managed without reference to the esophageal pressure measurements, and instead will follow an empiric high PEEP mechanical ventilation strategy. PEEP and FiO2 will be raised or lowered to achieve the oxygenation target level specified in a study table.
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Other: High PEEP mechanical ventilation |
Primary Outcome Measures :
- A composite outcome of mortality and time off the ventilator at 28-days. [ Time Frame: Day 28 ]The trial will utilize a primary composite endpoint that incorporates death and days off the ventilator at 28 days in such a manner that death constitutes a more serious outcome. Every subject is compared to every other subject in the trial and assigned one number resulting from each comparison. Since mortality outcome is clinically more important, mortality takes precedence over days off the ventilator. The sum of scores for patients in the treatment group is compared to the sum of scores of subjects in the control group to form a test statistic by the Mann-Whitney technique.
Secondary Outcome Measures :
- Ventilator free days to day 28 [ Time Frame: Day 28 ]Number of calendar days breathing unassisted.
- mortality [ Time Frame: Day 60 ]Hospital and ICU mortality to day 60
- lengths of stay [ Time Frame: Day 60 ]Hospital and ICU lengths of stay to days 28 and 60
- biomarkers of lung injury [ Time Frame: Day 7 ]Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment
- Survival [ Time Frame: 1 year ]Mortality to 1 year
- Need for rescue therapy [ Time Frame: Day 28 ]Rescue measures will be chosen according to the practice at the clinical site, and may include repeated recruitment maneuvers, prone positioning, nitric oxide, epoprostenol sodium, airway pressure release ventilation, high frequency ventilation, or ECMO.
- Activities of daily living [ Time Frame: 1 year ]Will assess via questionnaire (Barthel Index) done by phone at 1 year. Barthel Index scores range from 0-100, with 100 representing greatest independence of activities of daily living.
- Self-reported health assessment [ Time Frame: 1 year ]Will assess via questionnaire (12-Item Short-Form Health Survey [SF-12]) done by phone at 1 year. The SF-12 scores range from 0-100 points, with higher scores representing the highest level of health.
- Frailty in patients age 65 and older [ Time Frame: 1 year ]Will assess via questionnaire (Vulnerable Elders-13 Survey) done by phone at 1 year. VES scores range from 0-10 points, with higher scores representing greater risk.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:
- Hypoxemic respiratory failure with PaO2 / FIO2 ratio < 200 mmHg
- b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days
- Respiratory failure not fully explained by cardiac failure or fluid overload
- Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O
- Age 16 years or older
- Duration of ARDS 36 hours or less from meeting final Berlin criterion.
Exclusion Criteria:
- Received mechanical ventilation more than 96 hours
- Recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement
- Severe coagulopathy (platelet count < 5000/microliter or INR > 4)
- History of lung transplantation
- Elevated intracranial pressure or conditions where hypercapnia-induced elevations in intracranial pressure should be avoided
- Evidence of active air leak from the lung
- not committed to full support
- Participation in other intervention trials for ARDS or for sepsis within the past 30 days.
- Neuromuscular disease that impairs ability to ventilate spontaneously
- Severe chronic liver disease, defined as Child-Pugh Score of ≥12
- Treating clinician refusal, or unwillingness to commit to controlled ventilation for at least 24 hours
- Inability to get informed consent from the patient or surrogate.
- Use of rescue therapies for prior to enrollment (e.g. nitric oxide, ECMO, prone positioning, high frequency oscillation). This does not exclude cases where these therapies were used as the initial mode of ventilation
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01681225
Locations
| United States, California | |
| University of California at San Diego | |
| La Jolla, California, United States, 92093 | |
| Stanford University Medical Center | |
| Stanford, California, United States, 94305 | |
| United States, Florida | |
| Orlando Health | |
| Orlando, Florida, United States, 32806 | |
| United States, Maryland | |
| Shock-Trauma University of Maryland Medical Center | |
| Baltimore, Maryland, United States, 21201 | |
| United States, Massachusetts | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| Beth Israel Deaconess Medical Center | |
| Boston, Massachusetts, United States, 02215 | |
| University of Massachusets Medical Center | |
| Worcester, Massachusetts, United States, 01655 | |
| United States, Michigan | |
| University of Michigan | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| United States, New York | |
| Montefiore Medical Center | |
| Bronx, New York, United States, 10467 | |
| Canada, British Columbia | |
| Vancouver General Hospital | |
| Vancouver, British Columbia, Canada | |
| Canada, Ontario | |
| St Joseph's Healthcare | |
| Hamilton, Ontario, Canada, L8N 4A6 | |
| University Health Network | |
| Toronto, Ontario, Canada, M5G 2C4 | |
| Canada, Quebec | |
| Laval University | |
| Quebec City, Quebec, Canada, G1V 4G5 | |
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
| Principal Investigator: | Daniel S Talmor, MD, MPH | Beth Israel Deaconess Medical Center |
Publications of Results:
Other Publications:
Other Publications:
| Responsible Party: | Daniel Talmor, Edward Lowenstein Professor of Anaesthesia, Beth Israel Deaconess Medical Center |
| ClinicalTrials.gov Identifier: | NCT01681225 |
| Other Study ID Numbers: |
2009P000374 UM1HL108724 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 7, 2012 Key Record Dates |
| Last Update Posted: | December 3, 2019 |
| Last Verified: | December 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Daniel Talmor, Beth Israel Deaconess Medical Center:
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ARDS mechanical ventilation ALI esophageal pressure |
Additional relevant MeSH terms:
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Respiratory Distress Syndrome Respiratory Distress Syndrome, Newborn Acute Lung Injury Lung Diseases Respiratory Tract Diseases |
Respiration Disorders Infant, Premature, Diseases Infant, Newborn, Diseases Lung Injury |