scholarly journals The Esophageal Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of mechanical ventilation guided by transpulmonary pressure

BMJ Open ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. e006356 ◽  
Author(s):  
Emily Fish ◽  
Victor Novack ◽  
Valerie M Banner-Goodspeed ◽  
Todd Sarge ◽  
Stephen Loring ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mechanical Ventilation ◽  
Study Participant ◽  
Transpulmonary Pressure ◽  
Esophageal Pressure ◽  
Public Access ◽  
High Peep ◽  
Lower Tidal Volume ◽  
Study Participants ◽  
The Impact

IntroductionOptimal ventilator management for patients with acute respiratory distress syndrome (ARDS) remains uncertain. Lower tidal volume ventilation appears to be beneficial, but optimal management of positive end-expiratory pressure (PEEP) remains unclear. The Esophageal Pressure-Guided Ventilation 2 Trial (EPVent2) aims to examine the impact of mechanical ventilation directed at maintaining a positive transpulmonary pressure (PTP) in patients with moderate-to-severe ARDS.Methods and analysisEPVent2 is a multicentre, prospective, randomised, phase II clinical trial testing the hypothesis that the use of a PTP-guided ventilation strategy will lead to improvement in composite outcomes of mortality and time off the ventilator at 28 days as compared with a high-PEEP control. This study will enrol 200 study participants from 11 hospitals across North America. The trial will utilise a primary composite end point that incorporates death and days off the ventilator at 28 days to test the primary hypothesis that adjusting ventilator pressure to achieve positive PTP values will result in improved mortality and ventilator-free days.Ethics and disseminationSafety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approvals of the protocol as well as informed consent documents were also obtained from the Institutional Review Board of each participating institution prior to enrolling study participants at each respective site. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to PubMed Central in accordance with the National Institute of Health Public Access Policy.Trial registration numberClinicalTrials.gov under number NCT01681225.

The impact of sharing results of a randomized breast cancer clinical trial with study participants

2008 ◽  
Vol 115 (1) ◽  
pp. 123-129 ◽  
Author(s):  
Ann H. Partridge ◽  
A. C. Wolff ◽  
P. K. Marcom ◽  
P. A. Kaufman ◽  
L. Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Cancer Clinical Trial ◽  
Study Participants ◽  
The Impact

scholarly journals Under consent: participation of people with HIV in an Ebola vaccine trial in Canada

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Pierre-Marie David ◽  
Benjamin Mathiot ◽  
Oumy Thiongane ◽  
Janice E. Graham
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Vaccine Trial ◽  
Study Participant ◽  
Trial Participation ◽  
Structured Interviews ◽  
Contextual Diversity ◽  
Healthcare Needs ◽  
Study Participants ◽  
Trial Participants

Abstract Background Little is known about volunteers from Northern research settings who participate in vaccine trials of highly infectious diseases with no approved treatments. This article explores the motivations of HIV immunocompromised study participants in Canada who volunteered in a Phase II clinical trial that evaluated the safety and immunogenicity of an Ebola vaccine candidate. Methods Observation at the clinical study site and semi-structured interviews employing situational and discursive analysis were conducted with clinical trial participants and staff over one year. Interviews were recorded, transcribed and analysed using critical qualitative interpretivist thematic analytical techniques. Patterns were identified, clustered and sorted to generate distinct and comprehensive themes. We then reassembled events and contexts from the study participants’ stories to develop two ideal portraits based on "composite characters" based on study participants features. These provide ethnographically rich details of participants’ meaningful social worlds while protecting individual identities. Results Ten of the 14 clinical trial participants, and 3 study staff were interviewed. Participant demographics and socio-economic profiles expressed limited contextual diversity. Half were men who have sex with men, half were former injection drug users experiencing homelessness, one was female, none were racialized minorities and there were no people from HIV endemic countries. Fully 90% had previous involvement in other clinical studies. Their stories point to particular socio-economic situations that motivated their participation as clinical labor through trial participation. Conclusions Our findings support Fisher’s argument of “structural coercion” in clinical trial recruitment of vulnerable individuals experiencing precarious living conditions. Clinical trials should provide more detail of the structural socio-economic conditions and healthcare needs which lie “under consent” of study participants. Going well beyond an overly convenient narrative of altruism, ethical deliberation frameworks need to sufficiently address the structural conditions of clinical trials. We offer concrete possibilities for this and acknowledge that further research and clinical data should be made available underlying study participant contexts with regards to recruitment and participation in resource poor settings, in both the South and the North.

scholarly journals Mechanical Ventilation Guided by Uncalibrated Esophageal Pressure May Be Potentially Harmful

2020 ◽  
Vol 133 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Gianmaria Cammarota ◽  
Gianluigi Lauro ◽  
Erminio Santangelo ◽  
Ilaria Sguazzotti ◽  
Raffaella Perucca ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Robotic Surgery ◽  
Chest Wall ◽  
Clinical Setting ◽  
Intrathoracic Pressure ◽  
Esophageal Pressure ◽  
Esophageal Balloon ◽  
Manufacturer Recommendation ◽  
Pressure Swing ◽  
The Impact

Background Esophageal balloon calibration was proposed in acute respiratory failure patients to improve esophageal pressure assessment. In a clinical setting characterized by a high variability of abdominal load and intrathoracic pressure (i.e., pelvic robotic surgery), the authors hypothesized that esophageal balloon calibration could improve esophageal pressure measurements. Accordingly, the authors assessed the impact of esophageal balloon calibration compared to conventional uncalibrated approach during pelvic robotic surgery. Methods In 30 adult patients, scheduled for elective pelvic robotic surgery, calibrated end-expiratory and end-inspiratory esophageal pressure, and the associated respiratory variations were obtained at baseline, after pneumoperitoneum–Trendelenburg application, and with positive end-expiratory pressure (PEEP) administration and compared to uncalibrated values measured at 4-ml filling volume, as per manufacturer recommendation. Data are expressed as median and [25th, 75th percentile]. Results Ninety calibrations were successfully performed. Chest wall elastance worsened with pneumoperitoneum–Trendelenburg and PEEP (19.0 [15.5, 24.6] and 16.7 [11.4, 21.7] cm H2O/l) compared to baseline (8.8 [6.3, 9.8] cm H2O/l; P < 0.0001 for both comparisons). End-expiratory and end-inspiratory calibrated esophageal pressure progressively increased from baseline (3.7 [2.2, 6.0] and 7.7 [5.9, 10.2] cm H2O) to pneumoperitoneum–Trendelenburg (6.2 [3.8, 10.2] and 16.1 [13.1, 20.6] cm H2O; P = 0.014 and P < 0.001) and PEEP (8.8 [7.7, 15.6] and 18.9 [16.3, 22.0] cm H2O; P < 0.0001 vs. baseline for both comparison; P < 0.001 and P = 0.002 vs. pneumoperitoneum–Trendelenburg) and, at each study step, they were persistently lower than uncalibrated esophageal pressure (P < 0.0001 for all comparisons). Overall, difference among uncalibrated and calibrated esophageal pressure was 5.1 [3.8, 8.4] cm H2O at end-expiration and 3.8 [3.0, 6.3] cm H2O at end-inspiration. Uncalibrated esophageal pressure swing was always lower than calibrated one (P < 0.0001 for all comparisons) with a difference of −1.0 [−1.8, −0.4] cm H2O. Conclusions In a clinical setting with variable chest wall mechanics, uncalibrated measurements substantially overestimated absolute values and underestimated respiratory variations of esophageal pressure. Calibration could substantially improve mechanical ventilation guided by esophageal pressure. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Protective PEEP and Lung Capacity May Be Determined by a Rapid PEEP-step Procedure

2021 ◽  
Author(s):  
Christina Grivans ◽  
Ola Stenqvist
Keyword(s):  
Tidal Volume ◽  
Peep Level ◽  
Transpulmonary Pressure ◽  
Esophageal Pressure ◽  
Plateau Pressure ◽  
Lung Compliance ◽  
Driving Pressure ◽  
High Peep ◽  
Step Procedure ◽  
Protective Ventilation Strategy

Abstract Background: A protective ventilation strategy should be based on assessment of lung mechanics and transpulmonary pressure, as this is the pressure that directly “hits” the lung. Esophageal pressure has been used for this purpose but has not gained widespread clinical acceptance. Instead, respiratory system mechanics and airway driving pressure have been used as surrogate measures. We have shown that the lung P/V curve coincides with the line connecting the end-expiratory airway P/V points of a PEEP trial. Consequently, transpulmonary pressure increases as much as PEEP is increased. If the change in end-expiratory lung volume (ΔEELV) is determined, lung compliance (CL) can be determined as ΔEELV/ΔPEEP and ΔPTP as tidal volume times ΔPEEP/ΔEELV. Methods: In ten patients with acute respiratory failure, ΔEELV was measured during each 4 cmH2O PEEP-step from 0 to 16 cmH2O and CL for each PEEP interval calculated as ΔEELV/ΔPEEP giving a lung P/V curve for the whole PEEP trial. Results: Lung P/V curves showed a marked individual variation with an overall lung compliance of 43–143 ml/cmH2O (total inspiratory volume divided by end-inspiratory transpulmonary plateau pressure at PEEP 16 cmH2O). The two patients with lowest lung compliance were non-responders to PEEP with decreasing lung compliance at high PEEP levels, indicating over-distension. Patients with higher lung compliance had a positive response to PEEP with successively higher lung compliance when increasing PEEP. A two-step PEEP procedure starting from a clinical PEEP level of 8 cmH2O gave almost identical lung P/V curves as the four PEEP-step procedure. The ratio of airway driving pressure (ΔPAW) to transpulmonary driving pressure (ΔPTP/ΔPAW) varied between patients and changed with PEEP, reducing the value of ΔPAW as surrogate for ΔPTP in individual patients. Conclusion: Separation of lung and chest wall mechanics can be achieved without esophageal pressure measurements if ΔEELV is determined when PEEP is changed . Only a two-step PEEP procedure is required for obtaining a lung P/V curve from baseline clinical PEEP to end-inspiration at the highest PEEP level, which can be used to determine the PEEP level where transpulmonary driving pressure is lowest and possibly least injurious for any given tidal volume.Trial registration: ClinicalTrials.gov, NCT04484727. Registered 24 July 2020 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04484727?term=Lindgren%2C+Sophie&cntry=SE&draw=2&rank=1

scholarly journals Goal-Directed Mechanical Ventilation: Are We Aiming at the Right Goals? A Proposal for an Alternative Approach Aiming at Optimal Lung Compliance, Guided by Esophageal Pressure in Acute Respiratory Failure

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Arie Soroksky ◽  
Antonio Esquinas
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Chest Wall ◽  
Respiratory System ◽  
Transpulmonary Pressure ◽  
Esophageal Pressure ◽  
Plateau Pressure ◽  
Lung Compliance ◽  
Inspiratory Pressure

Patients with acute respiratory failure and decreased respiratory system compliance due to ARDS frequently present a formidable challenge. These patients are often subjected to high inspiratory pressure, and in severe cases in order to improve oxygenation and preserve life, we may need to resort to unconventional measures. The currently accepted ARDSNet guidelines are characterized by a generalized approach in which an algorithm for PEEP application and limited plateau pressure are applied to all mechanically ventilated patients. These guidelines do not make any distinction between patients, who may have different chest wall mechanics with diverse pathologies and different mechanical properties of their respiratory system. The ability of assessing pleural pressure by measuring esophageal pressure allows us to partition the respiratory system into its main components of lungs and chest wall. Thus, identifying the dominant factor affecting respiratory system may better direct and optimize mechanical ventilation. Instead of limiting inspiratory pressure by plateau pressure, PEEP and inspiratory pressure adjustment would be individualized specifically for each patient's lung compliance as indicated by transpulmonary pressure. The main goal of this approach is to specifically target transpulmonary pressure instead of plateau pressure, and therefore achieve the best lung compliance with the least transpulmonary pressure possible.

scholarly journals Obesity and Weaning from Mechanical Ventilation—An Exploratory Study

2018 ◽  
Vol 12 ◽  
pp. 117954841880100 ◽  
Author(s):  
Ogugua Ndili Obi ◽  
Mark Mazer ◽  
Charles Bangley ◽  
Zuheir Kassabo ◽  
Khalid Saadah ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Transpulmonary Pressure ◽  
Lung Compliance ◽  
Morbidly Obese ◽  
High Peep ◽  
Obese Adult ◽  
Institutional Review ◽  
Increased Risk ◽  
Significant Difference ◽  
Esophageal Balloon

Introduction: Obesity is associated with increased risk of hypercapnic respiratory failure, prolonged duration on mechanical ventilation, and extended weaning periods. Objective: Pilot study to determine whether morbidly obese adult tracheotomized subjects (body mass index [BMI] ⩾ 40) can be more efficiently weaned from the ventilator by optimizing their positive end-expiratory pressure (PEEP) using either an esophageal balloon or the best achieved static effective compliance. Methods: We randomly assigned 25 morbidly obese adult tracheotomized subjects (median [interquartile range] BMI 53.4 [26.4]; range 40.4-113.8) to 1 of 2 methods of setting PEEP; using either titration guided by esophageal balloon to overcome negative transpulmonary pressure (Ptp) (goal Ptp 0-5 cmH2O) (ESO group) or titration to maximize static effective lung compliance (Cstat group). Our outcomes of interest were number of subjects weaned by day 30 and time to wean. Results: At day 30, there was no significant difference in percentage of subjects weaned. 8/13 subjects (62%) in the ESO Group were weaned vs. 9/12(75%) in the Cstat Group ( P = 0.67). Among the 17 subjects who weaned, median time to ventilator liberation was significantly shorter in the ESO group: 3.5 days vs Cstat group 14 days ( P = .01). Optimal PEEP in the ESO and Cstat groups was similar (ESO mean ± SD = 26.5 ± 5.7 cmH2O and Cstat 24.2 ± 7 cmH2O ( P = .38). Conclusions: Optimization of PEEP using esophageal balloon to achieve positive transpulmonary pressure did not change the proportion of patients weaned. Among patients who weaned, use of the esophageal balloon resulted in faster liberation from mechanical ventilation. There were no adverse consequences of the high PEEP (mean 25.4; range 13-37 cmH2O) used in our study. The study was approved by the Institutional Review Board at our institution (UMCIRB#10-0343) and registered with clinicaltrials.gov (NCT02323009).

scholarly journals The impact of participant engagement activities in supporting dapivirine ring use among participants enrolled in the Phase III MTN-020/ASPIRE study

2021 ◽  
Author(s):  
Morgan Garcia ◽  
Ellen Luecke ◽  
Ashley Mayo ◽  
Rachel Scheckter ◽  
Patrick Ndase ◽  
...  
Keyword(s):  
Study Participant ◽  
Sub Saharan Africa ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Participant Engagement ◽  
Income Status ◽  
Adherence Support ◽  
Study Participants ◽  
The Impact

Abstract Background: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies for at-risk individuals, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. Methods: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Ring use was estimated based on residual dapivirine remaining in the last returned ring by each participant and connected to PEA attendance using participant identification numbers. We used multivariate logistic regression to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. Results: 2,312 of 2,629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (AOR=3.52) than those who never attended an event. There was an even stronger correlation between a last returned ring showing use and participant attendance at multiple events (AOR=4.03). Conclusions: Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

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