Percutaneous Temporary Placement of a Phrenic Nerve Stimulator for Diaphragm Pacing (RESCUE2)

A randomized clinical trial to investigate the use of the temporary Diaphragm Pacing Therapy System (DPTS) to rehabilitate the diaphragm in mechanically ventilated patients who have failed at least two weaning attempts. The goal is to strengthen and rehabilitate the diaphragm to liberate the patient more quickly from mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: Ventilator Induced Diaphragm Dysfunction
• Intervention / Treatment: Device: Diaphragmatic Pacing Therapy DPTS

Detailed Description

Mechanical ventilation (MV) is a life saving technology but can also cause damage to the lungs and diaphragm such as ventricular induced diaphragmatic dysfunction (VIDD). Research has shown that after being on mandatory MV and sedated the diaphragm begins to atrophy within as short as 18 hours. The Lungpacer Diaphragm Pacing Therapy System (DPTS) is a temporary therapy that consists of the Lungpacer IntraVenous Electrode Catheter (LIVE Catheter) and the Lungpacer Control Unit system. The LIVE Catheter is a proprietary central venous catheter that incorporates pacing electrodes in strategic areas that align with the left and right phrenic nerves. The LIVE Catheter can also be used for fluid delivery like any other central venous catheter. The randomized clinical trial will investigate the safety, effectiveness and performance of the Lungpacer DPTS. By stimulating the diaphragm through daily therapy sessions, with the intention of exercising and rehabilitating the diaphragm muscle so the patient may be able to be more quickly liberated from MV. The patient population includes those who have been mechanically ventilated for greater than or equal to 96 hours (4days), have failed two or more spontaneous breathing trials (SBT), and were not hypervolemic during the latest spontaneous breathing trial. Patients must have resolution of the initial indication for placement on mechanical ventilation before entering the trial.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU Angers, Reanimation Medicale
  • Colombes, France, 92700
    • Hôpital Louis-Mourier
  • Montpellier, France
    • CHU Montpellier
  • Nice, France, 06001
    • Centre Hospitalier Universitaire de Nice (CHU Nice)
  • Paris, France, 75015
    • Hôpital Européen Georges-Pompidou
  • Paris, France, 75651
    • Pitié Salpétrière Hospital
  • Strasbourg, France, 67000
    • Centre Hospitalier Universitaire CHU
• Germany
  • Aachen, Germany, 52074
    • Uniklinik RWTH Aachen
  • Bad Oeynhausen, Germany, 32545
    • Heart and Diabetes Center Bad Oeynhausen
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin - Mitte campus
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn
  • Dresden, Germany, 01307
    • Universitatsklinik Dresden
  • Gottingen, Germany, 37075
    • Universitätsmedizin Göttingen, Georg-August-Universität
  • Hamburg, Germany, 21075
    • Asklepios Kliniken Hamburg GmbH - Asklepios Klinikum Harburg
  • Hamburg, Germany
    • Universitätsklinikum Hamburg-Eppendorf (UKE)
  • Heidelberg, Germany, 69126
    • Med Uni-Heidelberg
  • Jena, Germany
    • Universitätsklinikum Jena
  • Nuernberg, Germany, 90419
    • Klinikum Nuernberg
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Schmallenberg, Germany
    • Fachkrankenhaus Kloster Grafschaft
  • Solingen, Germany, 42699
    • Wissenschaftliches Institut Bethanien für Pneumologie e.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or older
• have been mechanically ventilated for > or = to 96 hours (4 days), and
• have satisfied the Readiness-to-Wean criteria and
• have failed at least two VLTs, one of which is the study specific VLT.

Exclusion Criteria:

• currently on extracorporeal membrane oxygenation (ECMO);
• weaning failure due to hypervolemia;
• medical history or known anatomy that prevents insertion of the LIVE Catheter into the left subclavian vein;
• currently being treated with neuromuscular blockade;
• clinically overt congestive heart failure that is preventing weaning;
• pre-existing neuromuscular diseases that could affect the respiratory muscles;
• pre-existing severe chronic pulmonary fibrosis;
• pleural effusions occupying greater than one third of the pleural space on either side;
• BMI > or = 40;
• known or suspected phrenic nerve paralysis;
• any electrical device (implanted or external) that may be prone to interaction with or interference from the Lungpacer DPTS including neurological pacing/stimulator devices, cardiac pacemakers and defibrillators;
• prior bacteremia reported within the last 48 hours;
• current hemodynamic instability, sepsis or septic shock;
• terminally ill with 6 months or less life expectancy or not committed to full care;
• known or suspected to be pregnant or lactating; and
• currently being treated in another clinical trial studying an experimental treatment that could affect the study primary outcome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Diaphragm Pacing Therapy DPTS; Diaphragm Pacing intervention will be conducted 2x a day using the Diaphragmatic Pacing Therapy System (DPTS). The DPTS includes the Lungpacer IntraVenous Electrode Catheter (LIVE Catheter) which is inserted temporarily into the left subclavian vein, the Lungpacer Control Unit (LCU external unit) and an intermediate cable that connects the LCU to the LIVE Catheter.	Device: Diaphragmatic Pacing Therapy DPTS; Subjects will undergo DPTS 2 times a day until successfully extubated with no reintubation within 48 hours.; Other Names: DPTS; LIVE Catheter
No Intervention: Control Group; Standard of care treatment of weaning failure, no intervention is involved in this control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion successfully weaned by 30 days for subjects randomized to Treatment (Lungpacer DPTS) as compared to subjects randomized to Control.	"Successfully weaned" is defined as passing the protocol-specific Ventilator Liberation Trial (VLT), or removed from MV, and not reintubated (subjects with an oral or nasal, endotracheal tube) or returned to MV (subjects with a tracheostomy) within 48 hours	Patients will be allowed to stay in the study for up to 30 (+2 days of follow up for adverse events) days if not removed from mechanical ventilation sooner

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days on mechanical ventilation	Days on mechanical ventilation from randomization to removal from MV associated with successful weaning or Day 30, whichever comes first	from randomization to 30 days
Changes in diaphragmatic thickening fraction on diaphragm ultrasound	Evaluate difference in changes in diaphragmatic thickening fraction between study allocation groups from randomization to successful weaning or on day 30 whichever comes first;	to successful weaning or on day 30 which ever comes first.
Changes in MIP	Change in MIP from randomization to last available measure; Change in MIP over time from randomization (baseline).	to successful weaning, or on day 30, whichever comes first.
Change in MIP	Rate of MIP change per day from randomization (baseline) to last available measure;	to successful weaning, or on day 30 whichever comes first.
Changes in RSBI	Change in RSBI from randomization (baseline) to last available measure; Change in RSBI over time from randomization (baseline);	to successful weaning, or on day 30, whichever comes first
Change in RSBI	Rate of RSBI change per day from randomization (baseline) to last available measure;	to successful weaning, or on day 30, whichever comes first
Mortality	30-day mortality	on day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weaning from and re-installation of Mechanical Ventilation in both groups	Cessations and re-instatements of mechanical ventilation to Day 30 or Study Exit	from randomization to 30 days
Tracheostomy	Proportion of subjects tracheotomized from randomization to study exit	from randomization to 30 days
Ventilator settings	Pressure Support daily, to last available measure	from randomization to 30 days
Ventilator settings	PEEP daily, to last available measure	from randomization to 30 days
Ventilator settings	Ventilation Mode daily, to last available measure	from randomization to 30 days
Ventilator settings	Tidal Volume daily, to last available measure	from randomization to 30 days
Number of ICU admissions and discharges through D30 for both groups	ICU admissions and discharges to day 30	from randomization to 30 days
Number of hospital admissions and discharges through D30 for both groups	Hospital admissions and discharges to day 30.	from randomization to 30 days

Collaborators and Investigators

• Sponsor: Lungpacer Medical Inc.
• Collaborators: Syntactx
• Investigators: Study Director: Linda H Clark, BSN, Vice President of Clinical Affairs, Lungpacer Medical, Inc.

Publications and helpful links

General Publications

• Evans D, Shure D, Clark L, Criner GJ, Dres M, de Abreu MG, Laghi F, McDonagh D, Petrof B, Nelson T, Similowski T. Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial. Trials. 2019 Jan 17;20(1):60. doi: 10.1186/s13063-018-3171-9.
• Dres M, de Abreu MG, Merdji H, Muller-Redetzky H, Dellweg D, Randerath WJ, Mortaza S, Jung B, Bruells C, Moerer O, Scharffenberg M, Jaber S, Besset S, Bitter T, Geise A, Heine A, Malfertheiner MV, Kortgen A, Benzaquen J, Nelson T, Uhrig A, Moenig O, Meziani F, Demoule A, Similowski T; RESCUE-2 Study Group Investigators. Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients. Am J Respir Crit Care Med. 2022 May 15;205(10):1169-1178. doi: 10.1164/rccm.202107-1709OC.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2017
• Primary Completion (Actual): December 29, 2019
• Study Completion (Actual): January 30, 2020

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (Actual): March 30, 2017

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 11, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Diaphragm atrophy; VIDD; Weaning failure
• Other Study ID Numbers: P-200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Only investigators participating in this clinical trial will be able to see final de-identified participant data at the completion of the study and it will be available through the clinical research organization (CRO).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes