History of Changes for Study: NCT03887715

A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)

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Study Record Versions

Version	Submitted Date	Changes
1	March 21, 2019	None (earliest Version on record)
2	September 5, 2019	Study Status, Outcome Measures, Arms and Interventions, Study Design, Study Description and Oversight
3	October 3, 2019	Recruitment Status, Study Status, Contacts/Locations and Oversight
4	November 19, 2019	Contacts/Locations and Study Status
5	February 18, 2020	Study Status and Contacts/Locations
6	May 21, 2020	Contacts/Locations and Study Status
7	October 6, 2020	Contacts/Locations and Study Status
8	October 20, 2020	Contacts/Locations and Study Status
9	December 1, 2020	Contacts/Locations and Study Status
10	January 26, 2021	Contacts/Locations and Study Status
11	April 9, 2021	Contacts/Locations and Study Status
12	May 26, 2021	Study Status and Contacts/Locations
13	June 4, 2021	Contacts/Locations and Study Status
14	July 27, 2021	Contacts/Locations and Study Status
15	September 14, 2021	Contacts/Locations and Study Status
16	November 29, 2021	Contacts/Locations and Study Status
17	December 21, 2021	Contacts/Locations and Study Status
18	March 22, 2022	Contacts/Locations and Study Status
19	March 28, 2022	Contacts/Locations and Study Status
20	June 21, 2022	Contacts/Locations and Study Status
21	July 1, 2022	Contacts/Locations and Study Status
22	August 10, 2022	Contacts/Locations and Study Status
23	September 2, 2022	Contacts/Locations and Study Status
24	October 23, 2023	Contacts/Locations and Study Status
25	January 8, 2024	Contacts/Locations and Study Status
26	March 11, 2024	Study Status and Contacts/Locations

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	LND-300
Brief Title:	A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)
Official Title:	A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Secondary IDs:

Study Status


Record Verification:	March 2019
Overall Status:	Not yet recruiting
Study Start:	July 31, 2019
Primary Completion:	August 31, 2022 [Anticipated]
Study Completion:	December 31, 2030 [Anticipated]

First Submitted:	March 21, 2019
First Submitted that Met QC Criteria:	March 21, 2019
First Posted:	March 25, 2019 [Actual]

Last Update Submitted that Met QC Criteria:	March 21, 2019
Last Update Posted:	March 25, 2019 [Actual]

Sponsor/Collaborators


Sponsor:	LivaNova
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	No
U.S. FDA-regulated Device:	Yes
Unapproved/Uncleared Device:
Pediatric Postmarket Surveillance:
Data Monitoring:	Yes

Study Description

Brief Summary:

Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.

Detailed Description:

A prospective, multi-center, randomized, controlled, blinded trial of subjects implanted with VNS Therapy. Active treatment and no stimulation control are randomized, at least two weeks after implantation and observed for 12-months.

After completing the 12 month endpoint in the RCT portion of the study, all RECOVER subjects will transition into the prospective, open-label, longitudinal portion of the study. Subjects in the control arm of RECOVER will be activated after completing the 12 month endpoint.

After completion of enrollment in the RCT portion or meeting of interim success criterion (whichever comes first), new subjects may enroll directly into the open-label,prospective, longitudinal study. These subjects will participate in the study for approximately 5 years.

Conditions


Conditions:	Treatment Resistant Depression
Keywords:	VNS Depression TRD

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Not Applicable
Interventional Study Model:	Parallel Assignment
	1:1 randomization of active stimulation vs. no stimulation for 12 months post randomization.
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	1000 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Active Comparator: Active Group will have VNS activated 2 weeks post implant.	Device: Vagal Nerve Stimulation (VNS) VNS is an implantable device that delivers stimulation to the vagal nerve. Other Names: VNS
Sham Comparator: Control Group will be implanted with VNS but device is not activated for the first 12 months. After 12 months, this group can receive stimulation.	Device: Vagal Nerve Stimulation (VNS) VNS is an implantable device that delivers stimulation to the vagal nerve. Other Names: VNS

Outcome Measures


Primary Outcome Measures:
1.	Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response [ Time Frame: 12 months post randomization ] Percentage of subjects with at least a 50% reduction from baseline in MADRS total score at 12 months from randomization
2.	Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response [ Time Frame: Baseline up to 12 Months ] Time from randomization to the first observed MADRS response.
3.	Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission [ Time Frame: Baseline up to 12 Months ] Time from randomization to the first observed MADRS remission.
4.	Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response [ Time Frame: Baseline up to 12 Months ] Duration of MADRS response, defined as the number of consecutive months from first observed MADRS response to the first assessment of MADRS response relapse (defined by reduction from baseline is < 40%).
5.	Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission [ Time Frame: Baseline up to 12 Months ] Total amount of time (months) of subject in remission divided by the total months of study participation up to 12 months from randomization. Subjects discontinuing the study before the 12 months assessment will be considered as not in remission for each successive month after discontinuance.
6.	Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Response [ Time Frame: Baseline up to 12 Months ] Maximum duration of MADRS response, defined as the maximum number of consecutive months in response (only for subjects experiencing MADRS response).
7.	Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission [ Time Frame: Baseline up to 12 Months ] Duration of MADRS remission, defined as the number of consecutive months from first observed MADRS remission to the first assessment of MADRS remission relapse (defined score > 20).
8.	Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Remission [ Time Frame: Baseline up to 12 Months ] Maximum duration of MADRS remission, defined as the maximum number of consecutive months in remission (only for subjects experiencing MADRS remission).
9.	Assess all Adverse Events [ Time Frame: Implant to 12 Months ] All adverse events, with a focus on device or procedure-related serious adverse events.
10.	WHO Disability Assessment Schedule (WHODAS) Changes in scores over [ Time Frame: Baseline to 12 Months ]
11.	Health Outcome Scale (EQ-5D-L) Changes in scores over time [ Time Frame: Baseline to 12 Months ]
12.	Clinical Global Impressions Scale - Improvement (CGI-I) Response [ Time Frame: 12 months post randomization ] A CGI-I score ≤ 2 at 12 months from randomization. Subjects discontinuing the study before the 12 months assessment will be considered as not in response for each successive month after discontinuance.
13.	Sheehan Suicidality Tracking Scale (S-STS) Changes in Suicidality [ Time Frame: Implant to 12 Months ] Suicide attempts as measured by items #10 & #12 in S-STS scale

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have had at least four episodes of MDD, including the current episode. The patient's depressive illness meets a minimum criterion of four prior failed treatments of adequate dose and duration as measured by a tool designed for this purpose. The patient is experiencing a major depressive episode (MDE) as measured by a guideline recommended depression scale assessment tool on two visits, within a 45-day span prior to implantation of the VNS device. Patients must maintain a stable medication regimen for at least four weeks before device implantation. Exclusion Criteria: Current or lifetime history of psychotic features in any MDE; Current or lifetime history of schizophrenia or schizoaffective disorder; Current or lifetime history of any other psychotic disorder; Current or lifetime history of rapid cycling bipolar disorder; Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder; Current suicidal intent; or Treatment with another investigational device or investigational drugs.

Contacts/Locations


Central Contact Person:	Laura D Yates, BSN Telephone: 281-228-7433 Email: laura.yates@livanova.com
Central Contact Backup:	Jeff F Way, BS Telephone: 281-228-7394 Email: jeffrey.way@livanova.com
Study Officials:	Charles Conway, MD Principal Investigator Washington University School of Medicine
Locations:

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:	URL: https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=292 Description: CMS Decision Memo for Vagus Nerve Stimulation (VNS) for Treatment Resistant Depression
Available IPD/Information: