. 2019 Jan 17;20(1):60.

doi: 10.1186/s13063-018-3171-9.

Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial

Douglas Evans^{1

2}, Deborah Shure³, Linda Clark¹, Gerard J Criner⁴, Martin Dres⁵, Marcelo Gama de Abreu⁶, Franco Laghi⁷, David McDonagh⁸, Basil Petrof⁹, Teresa Nelson¹⁰, Thomas Similowski¹¹

Affiliations

¹ Lungpacer Medical Incorporated, Burnaby, BC, Canada.
² Lungpacer Medical, 260 Sierra Drive, Exton, PA, 19335, USA.
³ Deborah Shure MD PA, Miami, FL, USA.
⁴ Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
⁵ Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique and AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale du Département R3S, Paris, France.
⁶ Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁷ Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital Hines, Loyola University, Maywood, IL, USA.
⁸ Departments of Anesthesiology and Pain Management, Neurological surgery, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Meakins-Christie Laboratories, and Translational Research in Respiratory Diseases Program, McGill University Health Centre and Research Institute, Montreal, QC, Canada.
¹⁰ Technomics Research, LLC, Minneapolis, MN, USA.
¹¹ Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique and AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale du Département R3S, Paris, France. thomas.similowski@sorbonne-universite.fr.

PMID: 30654837
PMCID: PMC6337771
DOI: 10.1186/s13063-018-3171-9

Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial

Douglas Evans et al. Trials. 2019.

. 2019 Jan 17;20(1):60.

doi: 10.1186/s13063-018-3171-9.

Authors

Affiliations

¹ Lungpacer Medical Incorporated, Burnaby, BC, Canada.
² Lungpacer Medical, 260 Sierra Drive, Exton, PA, 19335, USA.
³ Deborah Shure MD PA, Miami, FL, USA.
⁴ Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
⁵ Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique and AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale du Département R3S, Paris, France.
⁶ Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁷ Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital Hines, Loyola University, Maywood, IL, USA.
⁸ Departments of Anesthesiology and Pain Management, Neurological surgery, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Meakins-Christie Laboratories, and Translational Research in Respiratory Diseases Program, McGill University Health Centre and Research Institute, Montreal, QC, Canada.
¹⁰ Technomics Research, LLC, Minneapolis, MN, USA.
¹¹ Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique and AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale du Département R3S, Paris, France. thomas.similowski@sorbonne-universite.fr.

PMID: 30654837
PMCID: PMC6337771
DOI: 10.1186/s13063-018-3171-9

Abstract

Background: Mechanical ventilation (MV) is a life-saving technology that restores or assists breathing. Like any treatment, MV has side effects. In some patients it can cause diaphragmatic atrophy, injury, and dysfunction (ventilator-induced diaphragmatic dysfunction, VIDD). Accumulating evidence suggests that VIDD makes weaning from MV difficult, which involves increased morbidity and mortality.

Methods and analysis: This paper describes the protocol of a randomized, controlled, open-label, multicenter trial that is designed to investigate the safety and effectiveness of a novel therapy, temporary transvenous diaphragm pacing (TTVDP), to improve weaning from MV in up to 88 mechanically ventilated adult patients who have failed at least two spontaneous breathing trials over at least 7 days. Patients will be randomized (1:1) to TTVDP (treatment) or standard of care (control) groups. The primary efficacy endpoint is time to successful extubation with no reintubation within 48 h. Secondary endpoints include maximal inspiratory pressure and ultrasound-measured changes in diaphragm thickness and diaphragm thickening fraction over time. In addition, observational data will be collected and analyzed, including 30-day mortality and time to discharge from the intensive care unit and from the hospital. The hypothesis to be tested postulates that more TTVDP patients than control patients will be successfully weaned from MV within the 30 days following randomization.

Discussion: This study is the first large-scale clinical trial of a novel technology (TTVDP) aimed at accelerating difficult weaning from MV. The technology tested provides the first therapy directed specifically at VIDD, an important cause of delayed weaning from MV. Its results will help delineate the place of this therapeutic approach in clinical practice and help design future studies aimed at defining the indications and benefits of TTVDP.

Trial registration: ClinicalTrials.gov, NCT03096639 . Registered on 30 March 2017.

Keywords: Diaphragm; Mechanical ventilation; Phrenic stimulation; Ventilator-induced diaphragmatic dysfunction; Weaning.

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Conflict of interest statement

Ethics approval and consent to participate

The RESCUE 2 study has been ethically approved by competent institutional bodies in the two participating countries. In France, a global authorization relevant for all study sites has been granted by the Comité de Protection des Personnes Sud-Est VI, Clermont-Ferrand, France (decision # dated November 9, 2017) and by the competent authority (Agence Nationale de Sécurité du Médicament et des produits de santé) on June 32,017. In Germany, the study has been approved by the central Ethics Committee RWTH Aachen (August 14, 2017), which is relevant for each participating center and the competent authority (Bundesinstitut fur Arzneimittel und Medizinprodukte (BfArM) on September 1, 2017. Written informed consent will be obtained from all patients participating in the study, as a mandatory prerequisite to inclusion.

Consent for publication

Not applicable.

Competing interests

DE reports personal fees from Lungpacer Medical Inc. during the conduct of the study and outside the submitted work. In addition, DE has multiple related patents issued and pending. DS reports personal fees from Lungpacer Medical Inc. during the conduct of the study. LC reports fees from Lungpacer Medical Inc. during the conduct of the study and other competing interests from Lungpacer Medical Inc. outside the submitted work. GJC reports grants from Boehringer Ingelheim, Novartis, AstraZeneca, Respironics, MedImmune, Actelion, Forest, Pearl, Ikaria, Aeris, PneumRx, and Pulmonx and other support from HGE Health Care Solutions, LLC, Almirall, Boehringer Ingelheim, and Holaira, all outside the submitted work. MD reports personal fees and non-financial support from Lungpacer Medical Inc. during the conduct of the study and personal fees and non-financial support from Pulsion Medical Systems outside the submitted work. MGA reports personal fees from Lungpacer Medical Inc. during the conduct of the study and grants and personal fees from Dräger Medical AG, GlaxoSmithKline (GSK), and GE Healthcare outside the submitted work. DMD reports other support as well as research funding and consulting fees from Lungpacer Medical Inc. during the conduct of the study. BJP reports personal fees from Lungpacer Medical Inc. during the conduct of the study. TN reports personal fees from Lungpacer Medical Inc. during the conduct of the study and personal fees from Lungpacer Medical Inc. outside the submitted work. TS reports personal fees from Lungpacer Medical Inc. during the conduct of the study and personal fees from AstraZeneca France, personal fees from Boehringer Ingelheim France, personal fees from GSK France, personal fees and non-financial support from Novartis France, personal fees from TEVA France, personal fees from Chiesi, personal fees from Pierre Fabre Médicament, and personal fees from Invacare France, outside the submitted work. In the domain of therapeutic phrenic stimulation, TS received honoraria from Synapse Biomedical to translate the DPS/NeurRx4 user’s manual from English to French in 2007, and from 2012 to 2016, Synapse Biomedical contributed to a fundraiser organized by TS to promote respiratory research. TS advised Synapse Biomedical about clinical protocols but did not receive any honoraria from this company. TS currently collaborates with another diaphragm pacing company (Neuroresp/Atrotech) in an advisory capacity, here also without any honoraria or any non-financial support. FL declares that he has no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
SPIRIT figure describing study procedures and assessments. *SOFA* sequential organ failure assessment, *RASS* Richmond Agitation-Sedation Scale, *MIP* maximal inspiratory pressure, *RSBI* rapid shallow breathing index

**Fig. 2**
Schematic representation of the Lungpacer LIVE® Catheter system providing temporary transvenous phrenic stimulation for diaphragm pacing (*LCU* Lungpacer Control Unit). Credit to Mr. Jean Allard

See this image and copyright information in PMC

References

1. Pfuntner A, Wier LM, Stocks C. Most frequent procedures performed in U.S. hospitals, 2011: Statistical Brief #165. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville: Agency for Healthcare Research and Quality; 2013. - PubMed
1. Wunsch H, Kramer A, Gershengorn HB. Validation of intensive care and mechanical ventilation codes in Medicare data. Crit Care Med. 2017;45(7):e711–e7e4. doi: 10.1097/CCM.0000000000002316. - DOI - PMC - PubMed
1. Zilberberg MD, de Wit M, Shorr AF. Accuracy of previous estimates for adult prolonged acute mechanical ventilation volume in 2020: update using 2000-2008 data. Crit Care Med. 2012;40(1):18–20. doi: 10.1097/CCM.0b013e31822e9ffd. - DOI - PubMed
1. Beitler JR, Malhotra A, Thompson BT. Ventilator-induced lung injury. Clin Chest Med. 2016;37(4):633–646. doi: 10.1016/j.ccm.2016.07.004. - DOI - PMC - PubMed
1. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2014;370(10):980. - PubMed

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Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial

Affiliations

Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical