Clinical trial NCT01143064: Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Injuries
Keywords: Brain Injury
Trauma
Lead sponsor: BHR Pharma, LLC
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
name: Syneos Health
First posted: 2010-06-14
Enrollment: 1195
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Glasgow Outcome Scale (GOS)
timeFrame: 6 months
Secondary outcomes:
measure: Mortality at Month 1
timeFrame: 1 month post injury
measure: Mortality at Month 6
timeFrame: 6 months post injury
measure: Glasgow Outcome Scale at 3 Months
timeFrame: Month 3
measure: Glasgow Outcome Scale - Extended (GOS-E)
timeFrame: 3 months and 6 months post injury
measure: Short Form (36) Health Survey (SF-36)
timeFrame: 3 months and 6 months post injury
measure: Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
timeFrame: Admission through post-infusion Day 6
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health System Hospital
state: Delaware
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Healthcare
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital of Cook County
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Springfield
country: United States
facility: Saint John's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Wishard Health Services
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hospital
state: Indiana
city: Des Moines
country: United States
facility: Mercy Medical Center
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Shreveport
country: United States
facility: LSU Health - Shreveport
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Saginaw
country: United States
facility: St. Mary's of Michigan
state: Michigan
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center Hospital Hill
state: Missouri
city: Springfield
country: United States
facility: Lester E. Cox Memorial Hospital
state: Missouri
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center Hospital
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University-Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Youngstown
country: United States
facility: St. Elizabeth Health Center
state: Ohio
city: Oklahoma City
country: United States
facility: OU Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital & Health Center
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: University of South Carolina School of Medicine
state: South Carolina
city: Johnson City
country: United States
facility: Johnson City Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Huntington
country: United States
facility: Marshall University Joan C. Edwards School of Medicine
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: General Roca
country: Argentina
facility: Hospital Francisco Lopez Lima
state: Rio Negro
city: Rosario
country: Argentina
facility: Hospital de Emergencias Clemente Alvarez (HECA)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Hospital Nacional "Profesor Alejandro Posadas"
city: Comodoro Rivadavia
country: Argentina
facility: Hospital Regional De Comodoro Rivadavia (HRCR)
city: Mendoza
country: Argentina
facility: Hospital Central de Mendoza
city: Paraná
country: Argentina
facility: Hospital San Martin
city: Santa Fé
country: Argentina
facility: Hospital Dr. José Maria Cullen
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Salzburg
country: Austria
facility: Unfallkrankenhaus Salzburg
city: Vienna
country: Austria
facility: Landesklinikum Wiener Neustadt
city: Brussels
country: Belgium
facility: ULB Erasme
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg, Location Sint Jan
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Jette
country: Belgium
facility: University Hospital of the Free University Brussels (UZ Brussel)
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Chengdu
country: China
facility: Chengdu Military General Hospital
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Hangzhou
country: China
facility: The 2nd Affiliated Hospital of Zhejiang University
city: Jinan
country: China
facility: The Second Hospital of Shandong University
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
city: Shanghai
country: China
facility: Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Neurochirurgická klinika
city: Brno
country: Czechia
facility: Fakultní nemocnice u sv. Anny v Brnĕ, Neurochirurgická klinika
city: Plzeň
country: Czechia
facility: Fakultní Nemocnice Plzeň, Neurochirurgicé Oddĕlení
city: Praha
country: Czechia
facility: Fakultní nemocnice Kralovske Vinohrady
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin
city: Bron
country: France
facility: Hôpital Pierre Wertheimer
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble- Hópital Michallon
city: Lille
country: France
facility: CHRU de Lille- Hópital Roger Salengro
city: Limoges
country: France
facility: Centre Hospitalier Universitaire de Limoges
city: Marseille
country: France
facility: Centre Hospitalier Universitaire Hôpital Nord
city: Nancy
country: France
facility: Hópital Central - CHU de Nancy
city: Paris
country: France
facility: Groupe Hospitalier La Salpêtrière
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe-Universität
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Halle
country: Germany
facility: Berufsgenossenschaftliche Kliniken
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: Krankenhaus Merheim
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg gGmbH
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Osnabrück
country: Germany
facility: Niels-Stensen-Kliniken
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Budapest
country: Hungary
facility: Honvédelmi Minisztérium Állami Egészségügyi Központ
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Általános Orvostudományi Kar
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Petach-Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Milano
country: Italy
facility: Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
city: Milano
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Caritá
city: Rome
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Verona
country: Italy
facility: Azienda Ospedaliero Universitaria Integrata di Verona
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Timisoara
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Timisoara
city: Kemerovo
country: Russian Federation
facility: State Budget Educational Institution of Higher Professional Education "Kemerovskaya State Medical Academy of Federal Agency of Healthcare and Social Development"
city: Krasnoyarsk
country: Russian Federation
facility: 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"
city: Moscow
country: Russian Federation
facility: State Institution "Burdenko Neurosurgical Institute of RAMS"
city: Murmansk
country: Russian Federation
facility: State Healthcare Facility "Murmansk Regional Clinical Hospital n.a. Bayandin"
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg Healthcare Institution "City Mariinsky Hospital"
city: Yekaterinburg
country: Russian Federation
facility: State Institution of Health Care "Sverdlovsk Regional Clinical Hospital #1"
city: Singapore
country: Singapore
facility: National Neuroscience Institute
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Hebrón
city: Girona
country: Spain
facility: Hospital Universitario de Girona Dr. Josep Trueta
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrín
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario De Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fé de Valencia
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Hat yai
country: Thailand
facility: Faculty of Medicine, Prince of Songkla University
city: Khon Kaen
country: Thailand
facility: Khon Kaen Hospital
city: Fulwood
country: United Kingdom
facility: Royal Preston Hospital
state: Preston
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS, Leeds General Infirmary
city: London
country: United Kingdom
facility: The Royal London Hospital
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
Study officials:
affiliation: BHR Pharma, LLC
name: Neta R. Nelson, MPH
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.