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Brain InjuriesPhase 3SyNAPSeNCT01143064

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

A Phase 3 study testing Progesterone and Lipid emulsion without progesterone in people with Brain Injuries, run by BHR Pharma, LLC at 156 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 16 to 70 years
Conditions the study is for
Brain Injuries
What is being tested?
Progesterone and Lipid emulsion without progesterone
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,195 participants
Where
156 sitesin 21 countries
Study dates
Jun 2010to Mar 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or female patients between the age of 16 and 70 years, inclusive
  • Weight from 45 to 135 kg, inclusive
  • Sustained a closed head trauma no more than 8 hours before start of study drug infusion
  • TBI diagnosed by history and clinical examination
  • Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive
  • At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive)
  • 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)
  • Indication for ICP monitoring

Who cannot join

  • Life expectancy of less than 24 hours as determined by the Investigator
  • Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood pressure < 90 mmHg) at the time of randomization
  • Any spinal cord injury
  • Pregnancy
  • Penetrating head injury
  • Bilaterally fixed dilated pupils at the time of randomization
Show all 14Show fewer
  • Coma suspected to be primarily due to other causes (e.g. alcohol)
  • Pure epidural hematoma
  • Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome
  • Severe cardiac or hemodynamic instability prior to randomization
  • Known treatment with another investigational drug therapy or procedure within 30 days of injury
  • A history of allergic reaction to progesterone and related drugs or any of the components of the infusion
  • 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.
  • 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)

Trial locations and contacts

156 sites in 21 countries.

156 sites in 21 countries

United States53 sites
  • Summa Health System

    Akron, Ohio, 44304

  • Albany Medical Center Hospital

    Albany, New York, 12208

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Saint Alphonsus Regional Medical Center

    Boise, Idaho, 83706

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center

    Charlotte, North Carolina, 28203

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • John H. Stroger Jr. Hospital of Cook County

    Chicago, Illinois, 60612

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • University of Missouri Health Care

    Columbia, Missouri, 65212

  • University of South Carolina School of Medicine

    Columbia, South Carolina, 29203

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Delray Medical Center

    Delray Beach, Florida, 33431

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • Mercy Medical Center

    Des Moines, Iowa, 50314

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Texas Tech University Health Sciences Center

    El Paso, Texas, 79905

  • Marshall University Joan C. Edwards School of Medicine

    Huntington, West Virginia, 25701

  • Wishard Health Services

    Indianapolis, Indiana, 46202

  • Methodist Hospital

    Indianapolis, Indiana, 46206

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Johnson City Medical Center

    Johnson City, Tennessee, 37604

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Truman Medical Center Hospital Hill

    Kansas City, Missouri, 64108

  • LAC+USC Medical Center

    Los Angeles, California, 90033

  • University of Louisville Hospital

    Louisville, Kentucky, 40202

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • University of South Alabama Medical Center

    Mobile, Alabama, 36617

  • West Virginia University Hospital

    Morgantown, West Virginia, 26506

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

  • Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Christiana Care Health System Hospital

    Newark, Delaware, 19718

  • OU Medical Center

    Oklahoma City, Oklahoma, 73104

  • The Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Maine Medical Center

    Portland, Maine, 04102

  • Legacy Emanuel Hospital & Health Center

    Portland, Oregon, 97227

  • St. Mary's of Michigan

    Saginaw, Michigan, 48604

  • University of California San Diego Medical Center

    San Diego, California, 92103

  • LSU Health - Shreveport

    Shreveport, Louisiana, 71103

  • Saint John's Hospital

    Springfield, Illinois, 62769

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Lester E. Cox Memorial Hospital

    Springfield, Missouri, 65804

  • Tallahassee Memorial Healthcare

    Tallahassee, Florida, 32308

  • Tampa General Hospital

    Tampa, Florida, 33606

  • Westchester Medical Center

    Valhalla, New York, 10595

  • Wake Forest University-Baptist Medical Center

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts Memorial Medical Center

    Worcester, Massachusetts, 01655

  • St. Elizabeth Health Center

    Youngstown, Ohio, 44501

Other trials in United States

Spain12 sites
  • Hospital General Universitario de Alicante

    Alicante

  • Hospital Universitario Germans Trias i Pujol

    Badalona, Barcelona

  • Hospital Universitario de Bellvitge

    Barcelona

  • Hospital Universitario Vall Hebrón

    Barcelona

  • Hospital Universitario de Girona Dr. Josep Trueta

    Girona

  • Hospital Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitari Son Espases

    Palma de Mallorca

  • Hospital Parc Taulí

    Sabadell, Barcelona

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Clínico Universitario De Valencia

    Valencia

  • Hospital Universitari i Politecnic La Fé de Valencia

    Valencia

Other trials in Spain

Germany11 sites
  • Charité - Universitätsmedizin Berlin

    Berlin

  • Krankenhaus Merheim

    Cologne

  • Klinikum der J.W. Goethe-Universität

    Frankfurt

  • Universitätsmedizin Göttingen

    Göttingen

  • Berufsgenossenschaftliche Kliniken

    Halle

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg

  • Universitätsklinikum Heidelberg

    Heidelberg

  • Universitätsklinikum Gießen und Marburg gGmbH

    Marburg

  • Klinikum Nürnberg

    Nuremberg

  • Niels-Stensen-Kliniken

    Osnabrück

  • Universitätsklinikum Ulm

    Ulm

Other trials in Germany

China8 sites
  • Chengdu Military General Hospital

    Chengdu

  • The First Affiliated Hospital of Fujian Medical University

    Fuzhou

  • The 2nd Affiliated Hospital of Zhejiang University

    Hangzhou

  • The Second Hospital of Shandong University

    Jinan

  • Huashan Hospital of Fudan University

    Shanghai

  • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

    Shanghai

  • General Hospital of Tianjin Medical University

    Tianjin

  • The Affiliated Hospital of Xuzhou Medical College

    Xuzhou

Other trials in China

France8 sites
  • Groupe Hospitalier Pellegrin

    Bordeaux

  • Hôpital Pierre Wertheimer

    Bron

  • Centre Hospitalier Universitaire de Grenoble- Hópital Michallon

    La Tronche

  • CHRU de Lille- Hópital Roger Salengro

    Lille

  • Centre Hospitalier Universitaire de Limoges

    Limoges

  • Centre Hospitalier Universitaire Hôpital Nord

    Marseille

  • Hópital Central - CHU de Nancy

    Nancy

  • Groupe Hospitalier La Salpêtrière

    Paris

Other trials in France

Argentina7 sites
  • Hospital Nacional "Profesor Alejandro Posadas"

    Buenos Aires

  • Hospital Regional De Comodoro Rivadavia (HRCR)

    Comodoro Rivadavia

  • Hospital Francisco Lopez Lima

    General Roca, Río Negro Province

  • Hospital Central de Mendoza

    Mendoza

  • Hospital San Martin

    Paraná

  • Hospital de Emergencias Clemente Alvarez (HECA)

    Rosario, Santa Fe Province

  • Hospital Dr. José Maria Cullen

    Santa Fe

Other trials in Argentina

United Kingdom7 sites
  • Queen Elizabeth Hospital

    Birmingham

  • University Hospital Coventry

    Coventry

  • Royal Preston Hospital

    Fulwood, Preston

  • Leeds Teaching Hospitals NHS, Leeds General Infirmary

    Leeds

  • The Royal London Hospital

    London

  • The James Cook University Hospital

    Middlesbrough

  • Southampton University Hospital

    Southampton

Other trials in United Kingdom

Italy6 sites
  • Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

    Milan

  • Fondazione San Raffaele del Monte Tabor

    Milan

  • Azienda Ospedaliera San Gerardo

    Monza

  • Azienda Ospedaliero Universitaria Maggiore della Caritá

    Novara

  • Azienda Ospedaliera San Camillo Forlanini

    Rome

  • Azienda Ospedaliero Universitaria Integrata di Verona

    Verona

Other trials in Italy

Russia6 sites
  • State Budget Educational Institution of Higher Professional Education "Kemerovskaya State Medical Academy of Federal Agency of Healthcare and Social Development"

    Kemerovo

  • 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"

    Krasnoyarsk

  • State Institution "Burdenko Neurosurgical Institute of RAMS"

    Moscow

  • State Healthcare Facility "Murmansk Regional Clinical Hospital n.a. Bayandin"

    Murmansk

  • Saint Petersburg Healthcare Institution "City Mariinsky Hospital"

    Saint Petersburg

  • State Institution of Health Care "Sverdlovsk Regional Clinical Hospital #1"

    Yekaterinburg

Other trials in Russia

Belgium5 sites
  • ULB Erasme

    Brussels

  • Ziekenhuis Oost-Limburg, Location Sint Jan

    Genk

  • Universitair Ziekenhuis Gent

    Ghent

  • University Hospital of the Free University Brussels (UZ Brussel)

    Jette

  • University Hospital Gasthuisberg

    Leuven

Other trials in Belgium

Israel5 sites
  • Rambam Medical Center

    Haifa

  • Hadassah Medical Organization

    Jerusalem

  • Rabin Medical Center

    Petah Tikva

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

  • Chaim Sheba Medical Center

    Tel HaShomer

Other trials in Israel

Malaysia5 sites
  • Hospital Raja Permaisuri Bainun

    Ipoh

  • Hospital Kuala Lumpur

    Kuala Lumpur

  • University Malaya Medical Centre

    Kuala Lumpur

  • Hospital Tengku Ampuan Afzan

    Kuantan

  • Sarawak General Hospital

    Kuching

Other trials in Malaysia

Austria4 sites
  • Medizinische Universität Graz

    Graz

  • Medizinische Universität Innsbruck

    Innsbruck

  • Unfallkrankenhaus Salzburg

    Salzburg

  • Landesklinikum Wiener Neustadt

    Vienna

Other trials in Austria

Czechia4 sites
  • Fakultní nemocnice Brno Neurochirurgická klinika

    Brno

  • Fakultní nemocnice u sv. Anny v Brnĕ, Neurochirurgická klinika

    Brno

  • Fakultní Nemocnice Plzeň, Neurochirurgicé Oddĕlení

    Pilsen

  • Fakultní nemocnice Kralovske Vinohrady

    Prague

Other trials in Czechia

Hungary3 sites
  • Honvédelmi Minisztérium Állami Egészségügyi Központ

    Budapest

  • Pécsi Tudományegyetem Általános Orvostudományi Kar

    Pécs

  • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

    Szeged

Other trials in Hungary

Singapore3 sites
  • National Neuroscience Institute

    Singapore

  • National University Hospital

    Singapore

  • Singapore General Hospital

    Singapore

Other trials in Singapore

Thailand3 sites
  • Chiang Mai University

    Chiang Mai

  • Faculty of Medicine, Prince of Songkla University

    Hat Yai

  • Khon Kaen Hospital

    Khon Kaen

Other trials in Thailand

Netherlands2 sites
  • VU Medisch Centrum

    Amsterdam

  • Universitair Medisch Centrum Groningen

    Groningen

Other trials in Netherlands

Taiwan2 sites
  • Taichung Veterans General Hospital

    Taichung

  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

Finland1 site
  • Tampere University Hospital

    Tampere

Other trials in Finland

Romania1 site
  • Spitalul Clinic Judetean de Urgenta Timisoara

    Timișoara

Other trials in Romania

About this study

Official title: 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.

Conditions
Brain Injuries
Being tested
Progesterone, Lipid emulsion without progesterone
Keywords
Brain Injury, Trauma
Medical subject headings
Brain Injuries, Wounds and Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ProgesteroneDrug

    Also called BHR-100

    Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.

  • Lipid emulsion without progesteroneDrug

    Intravenous administration equal to 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.

Study groups in NCT01143064
Study groupRoleWhat they receive
ProgesteroneActive comparatorNot described
Receives: Drug: Progesterone
Lipid emulsion without progestronePlacebo comparatorNot described
Receives: Drug: Lipid emulsion without progesterone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Glasgow Outcome Scale (GOS)

    The GOS assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead.

    Measured: 6 months

Secondary outcomes (6)
  1. Mortality at Month 1

    The mortality rate at one month will be compared between the two treatment groups.

    Measured: 1 month post injury

  2. Mortality at Month 6

    The mortality rate at six months will be compared between the two treatment groups.

    Measured: 6 months post injury

  3. Glasgow Outcome Scale at 3 Months

    The GOS assesses the mortality and disability in traumatic brain injury patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State, or Dead.

    Measured: Month 3

  4. Glasgow Outcome Scale - Extended (GOS-E)

    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

    Measured: 3 months and 6 months post injury

  5. Short Form (36) Health Survey (SF-36)

    The Short Form (36) Health Survey (SF-36) is a validated survey of patient health consisting of eight scaled scores which are the weighted sums of the questions in their section. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, role physical, role emotional, role mental and mental health. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

    Measured: 3 months and 6 months post injury

  6. Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)

    Cerebral Perfusion Pressure (CPP) levels are presented according to clinically significant cut-off values. CPP was calculated from intracranial pressures and mean arterial pressures measured from Day through Day 6 after initiation of study medication, if an ICP monitor was in place. Specific therapies received during Days 1-6 are summarized according to the Therapeutic Intensity Level (TIL) by treatment group, as maximum level of therapy administered to the subject.

    Measured: Admission through post-infusion Day 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionMar 2014
  4. Study completionMar 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,195 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01143064
Sponsor's protocol ID
BHR-100-301
Other IDs
2010-018283-16
Acronym
SyNAPSe
Status last verified
Sep 2024
First submitted
10 Jun 2010
Last updated
2 Oct 2024
Data monitoring committee
Yes

Publications

  • Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007 Apr;49(4):391-402, 402.e1-2. doi: 10.1016/j.annemergmed.2006.07.932. Epub 2006 Sep 29.

    PubMed 17011666
  • Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care. 2008;12(2):R61. doi: 10.1186/cc6887. Epub 2008 Apr 30.

    PubMed 18447940
  • Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, Nelson NR, Stocchetti N; SYNAPSE Trial Investigators. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014 Dec 25;371(26):2467-76. doi: 10.1056/NEJMoa1411090. Epub 2014 Dec 10.

    PubMed 25493978

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Progesterone and Lipid emulsion without progesterone in people with Brain Injuries, run by BHR Pharma, LLC at 156 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 156 sites in United States, Spain, Germany, China, France and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Glasgow Outcome Scale (GOS) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01143064, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2024.

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