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Study of EG-1962 Compared to Standard of Care Oral Nimodipine in Adults With Aneurysmal Subarachnoid Hemorrhage (NEWTON2)

Primary Purpose

Subarachnoid Hemorrhage, Aneurysmal

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
EG-1962 (nimodipine microparticles)
Enteral Nimodipine
Sponsored by
Edge Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Subarachnoid Hemorrhage, Aneurysmal focused on measuring Aneurysm, Ruptured, Nimodipine, Subarachnoid Hemorrhage

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Ruptured saccular aneurysm confirmed by angiography and repaired by neurosurgical clipping or endovascular coiling
  2. External ventricular drain in place
  3. Subarachnoid hemorrhage on computed tomography (CT) scan of grade 2-4 on the modified Fisher scale
  4. WFNS grade 2, 3, or 4

Exclusion Criteria:

  1. Major complication during aneurysm repair such as, but not limited to, massive intraoperative hemorrhage, brain swelling, arterial occlusion or inability to secure the ruptured aneurysm
  2. Angiographic vasospasm prior to randomization
  3. Evidence of a cerebral infarction with neurological deficit

Sites / Locations

  • University of Alabama at Birmingham Hospital
  • Dignity Health; St. Joseph's Hospital and Medical Center
  • University of California, San Francisco-Fresno
  • Keck Hospital of USC
  • Cedars-Sinai Medical Center
  • David Geffen School of Medicine at UCLA
  • UCSF
  • Yale New Haven Hospital (YNHH)
  • UF Health Shands Florida
  • Baptist Medical Center/Lyerly Neurosurgery
  • Mayo Clinic Florida
  • Tallahassee Neurological Clinic
  • Northwestern Memorial Hospital
  • University of Illinois Hospital and Health Sciences System
  • Rush University Medical Center
  • University of Kansas Medical Center
  • University of Kentucky Medical Center
  • University of Louisville Hospital
  • University of Maryland Medical Systems
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Henry Ford Hospital
  • Hackensack University Medical Center
  • Robert Wood Johnson University Hospital
  • University of New Mexico Hospital
  • Montefiore Medical Center
  • North Shore University Hospital
  • Icahn School of Medicine at Mount Sinai
  • Lenox Hill Hospital
  • University of Rochester Medical Center
  • UNC Hospitals Neuroscience Intensive Care Unit
  • Duke University Medical Pavilion
  • University Hospitals Case Medical Center
  • The Ohio State University Wexner Medical Center
  • Providence St. Vincent Medical Center
  • Oregon Health and Science University
  • Hospital of the University of Pennsylvania
  • Jefferson Hospital for Neuroscience
  • Allegheny General Hospital
  • UPMC Presbyterian Hospital
  • Medical University of South Carolina
  • Semmes Murphey Neurological Clinic
  • Inova Fairfax Medical Campus
  • VCU Medical Center
  • University of Washington, Harborview Medical Center
  • Royal Prince Alfred Hospital
  • Nepean Hospital
  • Royal Adelaide Hospital
  • Medizinische Universitat Innsbruck/Tirol Universitatsklinik fur Neurologie
  • University of Alberta Hospital/Mackenzie Health Sciences Centre
  • Vancouver General Hospital
  • St. Michael's Hospital
  • Centre Hospitalier de l'Universite de Montreal (CHUM), Hopital Notre Dame
  • Royal University Hospital
  • Faculty Hospital Hradec Kralove
  • Faculty Hospital Brno
  • Faculty Hospital Ostrava
  • Military University Hospital Prague
  • Tampere University Hospital
  • Helsinki University Hospital
  • Neuro Intensive Care Unit 102i; Campus Charite Mitte (CCM)
  • Universitatsklinikum Erlangen, Neurologische Klinik, Koptkliniken
  • Klinik für Neurochirurgie des Universitätsklinikum Essen
  • Klinik für Neurochirurgie, Zentrum der Neurologie und Neurochirurgie, Goethe-Universitätsklinikum Frankfurt am Main
  • Universitätsklinikum Hamburg Eppendorf, Klinik und Poliklinik für Neurochirurgie, Neues Klinikum
  • Neurochirurgische Klinik der Universität Heidelberg
  • Zentrum fur Neurochirurgie der Uniklinik Koln
  • Klinik und Poliklinik für Neurochirurgie des Universitatsklinikum Leipzig
  • Neurochirurgische Klinik, Universitatsmedizin Mannheim, Universität Heidelberg
  • Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitat Munchen
  • Neutochirurgische Klinik und Poliklinik des Universitatsklinikum Wurzburg
  • Queen Mary Hospital
  • Prince of Wales Hospital
  • Rabin Medical Center
  • Rambam Health Care Center
  • Hadassah Hebrew University Medical Center
  • Sheba Medical Center
  • Auckland City Hospital
  • National Neuroscience Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

EG-1962 Group

Enteral Nimodipine Group

Arm Description

1 dose of intraventricular EG-1962 (nimodipine microparticles) 600 mg Up to 21 days of placebo capsules/tablets

1 dose of intraventricular normal saline Up to 21 days of oral nimodipine capsules/tablets

Outcomes

Primary Outcome Measures

Proportion of subjects with a favorable outcome measured on the Extended Glasgow Outcome Scale [Primary Efficacy Endpoint]
Proportion of subjects with a favorable outcome measured on the Extended Glasgow Outcome Scale (GOSE) at Day 90

Secondary Outcome Measures

Proportion of subjects with favorable neurocognitive outcome measured by the Montreal Cognitive Assessment [Secondary Efficacy Endpoint]
Proportion of subjects with favorable neurocognitive outcome measured by the Montreal Cognitive Assessment (MoCA) at Day 90

Full Information

First Posted
May 26, 2016
Last Updated
July 24, 2018
Sponsor
Edge Therapeutics Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02790632
Brief Title
Study of EG-1962 Compared to Standard of Care Oral Nimodipine in Adults With Aneurysmal Subarachnoid Hemorrhage
Acronym
NEWTON2
Official Title
Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults With Aneurysmal Subarachnoid Hemorrhage
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
DMC review concluded study has a low probability of meeting its primary endpoint
Study Start Date
July 2016 (undefined)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Edge Therapeutics Inc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study compares EG-1962 to enteral nimodipine in the treatment of aneurysmal subarachnoid hemorrhage.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subarachnoid Hemorrhage, Aneurysmal
Keywords
Aneurysm, Ruptured, Nimodipine, Subarachnoid Hemorrhage

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
374 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EG-1962 Group
Arm Type
Experimental
Arm Description
1 dose of intraventricular EG-1962 (nimodipine microparticles) 600 mg Up to 21 days of placebo capsules/tablets
Arm Title
Enteral Nimodipine Group
Arm Type
Active Comparator
Arm Description
1 dose of intraventricular normal saline Up to 21 days of oral nimodipine capsules/tablets
Intervention Type
Drug
Intervention Name(s)
EG-1962 (nimodipine microparticles)
Intervention Description
Single intraventricular administration of EG-1962 via EVD and placebo capsules or tablets administered for up to 21 days
Intervention Type
Drug
Intervention Name(s)
Enteral Nimodipine
Intervention Description
Enteral Nimodipine capsules or tablets administered for up to 21 days and single intraventricular administration of saline via EVD
Primary Outcome Measure Information:
Title
Proportion of subjects with a favorable outcome measured on the Extended Glasgow Outcome Scale [Primary Efficacy Endpoint]
Description
Proportion of subjects with a favorable outcome measured on the Extended Glasgow Outcome Scale (GOSE) at Day 90
Time Frame
90 Days
Secondary Outcome Measure Information:
Title
Proportion of subjects with favorable neurocognitive outcome measured by the Montreal Cognitive Assessment [Secondary Efficacy Endpoint]
Description
Proportion of subjects with favorable neurocognitive outcome measured by the Montreal Cognitive Assessment (MoCA) at Day 90
Time Frame
90 Days
Other Pre-specified Outcome Measures:
Title
Adverse Events
Description
Incidence and severity of adverse events in EG-1962 treated subjects compared to subjects treated with standard of care oral nimodipine
Time Frame
90 Days
Title
Delayed Cerebral Infarction
Description
Proportion of subjects with delayed cerebral infarction present on CT scan at Day 30
Time Frame
30 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ruptured saccular aneurysm confirmed by angiography and repaired by neurosurgical clipping or endovascular coiling External ventricular drain in place Subarachnoid hemorrhage on computed tomography (CT) scan of grade 2-4 on the modified Fisher scale WFNS grade 2, 3, or 4 Exclusion Criteria: Major complication during aneurysm repair such as, but not limited to, massive intraoperative hemorrhage, brain swelling, arterial occlusion or inability to secure the ruptured aneurysm Angiographic vasospasm prior to randomization Evidence of a cerebral infarction with neurological deficit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R. Loch Macdonald, MD, PhD
Organizational Affiliation
Edge Therapeutics Inc
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Dignity Health; St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
University of California, San Francisco-Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93701
Country
United States
Facility Name
Keck Hospital of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Yale New Haven Hospital (YNHH)
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
UF Health Shands Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Baptist Medical Center/Lyerly Neurosurgery
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Tallahassee Neurological Clinic
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Illinois Hospital and Health Sciences System
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612-7232
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Kentucky Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
University of Louisville Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Maryland Medical Systems
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Robert Wood Johnson University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
University of New Mexico Hospital
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Lenox Hill Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10075
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
UNC Hospitals Neuroscience Intensive Care Unit
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Pavilion
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Providence St. Vincent Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Jefferson Hospital for Neuroscience
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
UPMC Presbyterian Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston Air Force Base
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Semmes Murphey Neurological Clinic
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Inova Fairfax Medical Campus
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
VCU Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Washington, Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Nepean Hospital
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
02747
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
Facility Name
Medizinische Universitat Innsbruck/Tirol Universitatsklinik fur Neurologie
City
Innsbruck
ZIP/Postal Code
06020
Country
Austria
Facility Name
University of Alberta Hospital/Mackenzie Health Sciences Centre
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z1M9
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
Centre Hospitalier de l'Universite de Montreal (CHUM), Hopital Notre Dame
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
Facility Name
Faculty Hospital Hradec Kralove
City
Hradec Králové
State/Province
Hradec Kralov
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Faculty Hospital Brno
City
Brno
State/Province
South Moravian Region
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Faculty Hospital Ostrava
City
Ostrava
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Military University Hospital Prague
City
Prague
ZIP/Postal Code
16902
Country
Czechia
Facility Name
Tampere University Hospital
City
Tampere
State/Province
Pirkanmaa
ZIP/Postal Code
33521
Country
Finland
Facility Name
Helsinki University Hospital
City
Helsinki
ZIP/Postal Code
00260
Country
Finland
Facility Name
Neuro Intensive Care Unit 102i; Campus Charite Mitte (CCM)
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitatsklinikum Erlangen, Neurologische Klinik, Koptkliniken
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Klinik für Neurochirurgie des Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Klinik für Neurochirurgie, Zentrum der Neurologie und Neurochirurgie, Goethe-Universitätsklinikum Frankfurt am Main
City
Frankfurt am Main
ZIP/Postal Code
60528
Country
Germany
Facility Name
Universitätsklinikum Hamburg Eppendorf, Klinik und Poliklinik für Neurochirurgie, Neues Klinikum
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Neurochirurgische Klinik der Universität Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Zentrum fur Neurochirurgie der Uniklinik Koln
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Klinik und Poliklinik für Neurochirurgie des Universitatsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04013
Country
Germany
Facility Name
Neurochirurgische Klinik, Universitatsmedizin Mannheim, Universität Heidelberg
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitat Munchen
City
Munchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Neutochirurgische Klinik und Poliklinik des Universitatsklinikum Wurzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Prince of Wales Hospital
City
New Kowloon
Country
Hong Kong
Facility Name
Rabin Medical Center
City
Petaẖ Tiqwa
State/Province
Petah-Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Rambam Health Care Center
City
Haifa
ZIP/Postal Code
3109606
Country
Israel
Facility Name
Hadassah Hebrew University Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
Country
Israel
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
National Neuroscience Institute
City
Singapore
ZIP/Postal Code
308433
Country
Singapore

12. IPD Sharing Statement

Citations:
PubMed Identifier
32138631
Citation
Carlson AP, Hanggi D, Wong GK, Etminan N, Mayer SA, Aldrich F, Diringer MN, Schmutzhard E, Faleck HJ, Ng D, Saville BR, Bleck T, Grubb R Jr, Miller M, Suarez JI, Proskin HM, Macdonald RL; NEWTON Investigators. Single-Dose Intraventricular Nimodipine Microparticles Versus Oral Nimodipine for Aneurysmal Subarachnoid Hemorrhage. Stroke. 2020 Apr;51(4):1142-1149. doi: 10.1161/STROKEAHA.119.027396. Epub 2020 Mar 6.
Results Reference
derived
PubMed Identifier
30014184
Citation
Hanggi D, Etminan N, Mayer SA, Aldrich EF, Diringer MN, Schmutzhard E, Faleck HJ, Ng D, Saville BR, Macdonald RL; NEWTON Investigators. Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]. Neurocrit Care. 2019 Feb;30(1):88-97. doi: 10.1007/s12028-018-0575-z.
Results Reference
derived

Learn more about this trial

Study of EG-1962 Compared to Standard of Care Oral Nimodipine in Adults With Aneurysmal Subarachnoid Hemorrhage

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