Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury (SyNAPSe)

June 11, 2014 updated by: BHR Pharma, LLC

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Investigate the Efficacy and Safety of Progesterone in Patients With Severe Traumatic Brain Injury

The SyNAPSe trial will study if giving intravenous (i.v.) progesterone within 8 hours of the injury for a total of 120 hours to severe traumatic brain injury patients improves their recovery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1195

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Mendoza, Argentina
        • Hospital Central de Mendoza
      • Paraná, Argentina
        • Hospital San Martín
      • Provincia de Buenos Aires, Argentina
        • Hospital Nacional "Profesor Alejandro Posadas"
      • Provincia de Chubut, Argentina
        • Hospital Regional De Comodoro Rivadavia (HRCR)
      • Santa Fé, Argentina
        • Hospital Dr. Jose Maria Cullen
    • Rio Negro
      • General Roca, Rio Negro, Argentina
        • Hospital Francisco Lopez Lima
    • Santa Fe
      • Rosario, Santa Fe, Argentina
        • Hospital de Emergencias Clemente Alvarez (HECA)
  • Austria
      • Graz, Austria
        • Medizinische Universität Graz
      • Innsbruck, Austria
        • Medizinische Universität Innsbruck
      • Salzburg, Austria
        • Unfallkrankenhaus Salzburg
      • Vienna, Austria
        • Landesklinikum Wiener Neustadt
  • Belgium
      • Brussels, Belgium
        • ULB Erasme
      • Genk, Belgium
        • Ziekenhuis Oost-Limburg, Location Sint Jan
      • Gent, Belgium
        • Universitair Ziekenhuis Gent
      • Jette, Belgium
        • University Hospital of the Free University Brussels (UZ Brussel)
      • Leuven, Belgium
        • University Hospital Gasthuisberg
  • China
      • Chengdu, China
        • Chengdu Military General Hospital
      • Fuzhou, China
        • The First Affiliated Hospital of Fujian Medical University
      • Hangzhou, China
        • The 2nd Affiliated Hospital of Zhejiang University
      • Jinan, China
        • The Second Hospital of Shandong University
      • Shanghai, China
        • Huashan Hospital of Fudan University
      • Shanghai, China
        • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Tianjin, China
        • General Hospital of Tianjin Medical University
      • Xuzhou, China
        • The Affiliated Hospital of Xuzhou Medical College
  • Czech Republic
      • Brno, Czech Republic
        • Fakultní nemocnice Brno Neurochirurgická klinika
      • Brno, Czech Republic
        • Fakultní nemocnice u sv. Anny v Brnĕ, Neurochirurgická klinika
      • Plzeň, Czech Republic
        • Fakultní Nemocnice Plzeň, Neurochirurgicé Oddĕlení
      • Praha, Czech Republic
        • Fakultni nemocnice Kralovske Vinohrady
  • Finland
      • Tampere, Finland
        • Tampere university Hospital
  • France
      • Bordeaux, France
        • Groupe Hospitalier Pellegrin
      • Bron, France
        • Hôpital Pierre Wertheimer
      • La Tronche, France
        • Centre Hospitalier Universitaire de Grenoble- Hópital Michallon
      • Lille, France
        • CHRU de Lille- Hópital Roger Salengro
      • Limoges, France
        • Centre hospitalier universitaire de Limoges
      • Marseille, France
        • Centre Hospitalier Universitaire Hôpital Nord
      • Nancy, France
        • Hópital Central - CHU de Nancy
      • Paris, France
        • Groupe Hospitalier La Salpétrière
  • Germany
      • Berlin, Germany
        • Charité - Universitätsmedizin Berlin
      • Frankfurt, Germany
        • Klinikum der J.W. Goethe-Universitat
      • Göttingen, Germany
        • Universitätsmedizin Göttingen
      • Halle, Germany
        • Berufsgenossenschaftliche Kliniken
      • Hamburg, Germany
        • Universitatsklinikum Hamburg-Eppendorf
      • Heidelberg, Germany
        • Universitätsklinikum Heidelberg
      • Köln, Germany
        • Krankenhaus Merheim
      • Marburg, Germany
        • Universitätsklinikum Gießen und Marburg gGmbH
      • Nürnberg, Germany
        • Klinikum Nürnberg
      • Osnabrück, Germany
        • Niels-Stensen-Kliniken
      • Ulm, Germany
        • Universitätsklinikum Ulm
  • Hungary
      • Budapest, Hungary
        • Honvédelmi Minisztérium Állami Egészségügyi Központ
      • Pécs, Hungary
        • Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar
      • Szeged, Hungary
        • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
  • Israel
      • Haifa, Israel
        • Rambam Medical Center
      • Jerusalem, Israel
        • Hadassah Medical Organization
      • Petach-Tikva, Israel
        • Rabin Medical Center
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center
      • Tel-Hashomer, Israel
        • Chaim Sheba Medical Center
  • Italy
      • Milano, Italy
        • Fondazione San Raffaele del Monte Tabor
      • Milano, Italy
        • Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
      • Monza, Italy
        • Azienda Ospedaliera San Gerardo
      • Novara, Italy
        • Azienda Ospedaliero Universitaria Maggiore della Carità
      • Rome, Italy
        • Azienda Ospedaliera San Camillo Forlanini
      • Verona, Italy
        • Azienda Ospedaliero Universitaria Integrata di Verona
  • Malaysia
      • Ipoh, Perak, Malaysia
        • Hospital Raja Permaisuri Bainun
      • Kuala Lumpur, Malaysia
        • University Malaya Medical Centre
      • Kuala Lumpur, Malaysia
        • Hospital Kuala Lumpur
      • Kuantan, Pahang, Malaysia
        • Hospital Tengku Ampuan Afzan
      • Kuching, Sarawak, Malaysia
        • Sarawak General Hospital
  • Netherlands
      • Amsterdam, Netherlands
        • VU Medisch Centrum
      • Groningen, Netherlands
        • Universitair Medisch Centrum Groningen
  • Romania
      • Timisoara, Romania
        • Spitalul Clinic Judetean de Urgenta Timisoara
  • Russian Federation
      • Kemerovo, Russian Federation
        • State Budget Educational Institution of Higher Professional Education "Kemerovskaya State Medical Academy of Federal Agency of Healthcare and Social Development"
      • Krasnoyarsk, Russian Federation
        • State Professional Institution of High Professional Education "Krasnoyarsk State Medical University named after Prof. V.F. Voyno-Yasenetsky of Ministry of Health and Social Development"
      • Moscow, Russian Federation
        • State Institution "Burdenko Neurosurgical Institute of RAMS"
      • Murmansk, Russian Federation
        • State Healthcare Facility "Murmansk Regional Clinical Hospital n.a. Bayandin"
      • St. Petersburg, Russian Federation
        • Saint Petersburg Healthcare Institution "City Mariinsky Hospital"
      • Yekaterinburg, Russian Federation
        • State Institution of Health Care "Sverdlovsk Regional Clinical Hospital #1"
  • Singapore
      • Singapore, Singapore
        • National University Hospital
      • Singapore, Singapore
        • Singapore General Hospital
      • Singapore, Singapore
        • National Neuroscience Institute
  • Spain
      • Alicante, Spain
        • Hospital General Universitario de Alicante
      • Barcelona, Spain
        • Hospital Universitario de Bellvitge
      • Barcelona, Spain
        • Hospital Universitario Vall Hebron
      • Girona, Spain
        • Hospital Universitario de Girona Dr. Josep Trueta
      • Las Palmas de Gran Canaria, Spain
        • Hospital Universitario de Gran Canaria Dr. Negrin
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Palma de Mallorca, Spain
        • Hospital Universitari Son Espases
      • Sevilla, Spain
        • Hospital Universitario Virgen Del Rocio
      • Valencia, Spain
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain
        • Hospital Universitari i Politecnic La Fe de Valencia
    • Barcelona
      • Badalona, Barcelona, Spain
        • Hospital Universitario Germans Trias i Pujol
      • Sabadell, Barcelona, Spain
        • Hospital Parc Tauli
  • Taiwan
      • Taichung, Taiwan
        • Taichung Veterans General Hospital
      • Taipei, Taiwan
        • National Taiwan University Hospital
  • Thailand
      • Chiang Mai, Thailand
        • Chiang Mai University
      • Hat yai, Thailand
        • Faculty of Medicine, Prince of Songkla University
      • Khon Kaen, Thailand
        • Khon Kaen Hospital
  • United Kingdom
      • Birmingham, United Kingdom
        • Queen Elizabeth Hospital
      • Coventry, United Kingdom
        • University Hospital Coventry
      • Leeds, United Kingdom
        • Leeds Teaching Hospitals NHS, Leeds General Infirmary
      • London, United Kingdom
        • The Royal London Hospital
      • Middlesbrough, United Kingdom
        • The James Cook University Hospital
      • Southampton, United Kingdom
        • Southampton University Hospital
    • Preston
      • Fulwood, Preston, United Kingdom
        • Royal Preston Hospital
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36617
        • University of South Alabama Medical Center
    • California
      • Los Angeles, California, United States, 90033
        • LAC+USC Medical Center
      • San Diego, California, United States, 92103
        • University of California San Diego Medical Center
    • Colorado
      • Denver, Colorado, United States, 80204
        • Denver Health Medical Center
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System Hospital
    • Florida
      • Delray Beach, Florida, United States, 33431
        • Delray Medical Center
      • Tallahassee, Florida, United States, 32308
        • Tallahassee Memorial HealthCare
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Regional Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • John H. Stroger Jr. Hospital of Cook County
      • Park Ridge, Illinois, United States, 60068
        • Advocate Lutheran General Hospital
      • Springfield, Illinois, United States, 62769
        • Saint John's Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Wishard Health Services
      • Indianapolis, Indiana, United States, 46206
        • Methodist Hospital
    • Iowa
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Hospital
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • LSU Health - Shreveport
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • Massachusetts
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Saginaw, Michigan, United States, 48604
        • St. Mary's of Michigan
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri Health Care
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Center Hospital Hill
      • Springfield, Missouri, United States, 65804
        • Lester E. Cox Memorial Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • The Nebraska Medical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Robert Wood Johnson University Hospital
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center Hospital
      • Valhalla, New York, United States, 10595
        • Westchester Medical Center
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Mission Hospital
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University-Baptist Medical Center
    • Ohio
      • Akron, Ohio, United States, 44304
        • SUMMA Health System
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
      • Youngstown, Ohio, United States, 44501
        • St. Elizabeth Health Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • OU Medical Center
    • Oregon
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital & Health Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Columbia, South Carolina, United States, 29203
        • University of South Carolina School of Medicine
    • Tennessee
      • Johnson City, Tennessee, United States, 37604
        • Johnson City Medical Center
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University Medical Center
    • Texas
      • El Paso, Texas, United States, 79905
        • Texas Tech University Health Sciences Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • Marshall University Joan C. Edwards School of Medicine
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients between the age of 16 and 70 years, inclusive
  2. Weight from 45 to 135 kg, inclusive
  3. Sustained a closed head trauma no more than 8 hours before start of study drug infusion
  4. TBI diagnosed by history and clinical examination
  5. Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive
  6. At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive)
  7. Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (diffuse injury II-IV, evacuated and non-evacuated mass lesion, Marshall's CT Classification)
  8. Indication for ICP monitoring

Exclusion Criteria:

  1. Life expectancy of less than 24 hours as determined by the Investigator
  2. Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood pressure < 90 mmHg) at the time of randomization
  3. Any spinal cord injury
  4. Pregnancy
  5. Penetrating head injury
  6. Bilaterally fixed dilated pupils at the time of randomization
  7. Coma suspected to be primarily due to other causes (e.g. alcohol)
  8. Pure epidural hematoma
  9. Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome
  10. Severe cardiac or hemodynamic instability prior to randomization
  11. Known treatment with another investigational drug therapy or procedure within 30 days of injury
  12. A history of allergic reaction to progesterone and related drugs or any of the components of the infusion
  13. Any disease, in the opinion of the Investigator, that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
  14. Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol through the final visit (6 months post-injury)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Progesterone
Drug: Progesterone
Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
Other Names:
  • BHR-100
PLACEBO_COMPARATOR: Lipid emulsion without progestrone
Drug: Lipid emulsion without progesterone
Intravenous administration equal to 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glasgow Outcome Scale (GOS)
Time Frame: 6 months
The GOS (Jennett and Bond, 1975) assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 1 month and 6 months post injury
The mortality rate at one and six months will be compared between the two treatment groups.
1 month and 6 months post injury
Glasgow Outcome Scale
Time Frame: Month 3
Month 3
Glasgow Outcome Scale - Extended (GOS-E)
Time Frame: 3 months and 6 months post injury

The GOS-E assessment of mortality and disability in TBI patients extends the original five GOS categories of functional outcome to eight categories:

  • Dead
  • Vegetative State
  • Lower Severe Disability
  • Upper Severe Disability
  • Lower Moderate Disability
  • Upper Moderate Disability
  • Lower Good Recovery
  • Upper Good Recovery
3 months and 6 months post injury
Short Form (36) Health Survey (SF-36)
Time Frame: 3 months and 6 months post injury

The SF-36 is a validated survey of patient health consisting of eight scaled scores. The eight sections are:

  • vitality
  • physical functioning
  • bodily pain
  • general health perceptions
  • role physical
  • role emotional
  • role mental
  • mental health

The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health.
3 months and 6 months post injury
Effect of progesterone on Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), and Therapeutic Intensity Level (TIL)
Time Frame: Admission through post-infusion Day 6
Admission through post-infusion Day 6
Effect of progesterone on the progression of intracranial pathology
Time Frame: Admission and Day 6 computed tomography (CT) scans
Admission and Day 6 computed tomography (CT) scans

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BHR Pharma, LLC

Collaborators

Syneos Health
PRA Health Sciences

Investigators

  • Study Director: Neta R. Nelson, MPH, BHR Pharma, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (ACTUAL)

March 1, 2014

Study Completion (ACTUAL)

March 1, 2014

Study Registration Dates

First Submitted

June 10, 2010

First Submitted That Met QC Criteria

June 10, 2010

First Posted (ESTIMATE)

June 14, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

June 19, 2014

Last Update Submitted That Met QC Criteria

June 11, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BHR-100-301
  • 2010-018283-16 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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