Study Stopped
futility: low conditional power to demonstrate benefit of progesterone
Progesterone for the Treatment of Traumatic Brain Injury III
ProTECT
Phase 3 Clinical Trial to Determine if Progesterone Along With Standard Medical Care for Brain Injury is More Effective at Limiting the Amount of Damage Cause by a Traumatic Brain Injury Than Standard Medical Care Alone.
2 other identifiers
interventional
882
1 country
36
Brief Summary
The ProTECT study will determine if intravenous (IV) progesterone (started within 4 hours of injury and given for a total of 96 hours), is more effective than placebo for treating victims of moderate to severe acute traumatic brain injury.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2010
Typical duration for phase_3
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2009
CompletedFirst Posted
Study publicly available on registry
January 15, 2009
CompletedStudy Start
First participant enrolled
March 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2014
CompletedResults Posted
Study results publicly available
July 3, 2015
CompletedJanuary 20, 2016
December 1, 2015
4.2 years
January 14, 2009
April 1, 2015
December 16, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE)
A measure of functional recovery: A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. Favorable outcome was defined via stratified dichotomy based on the severity of the initial injury. For subjects with a severe injury, a GOS-E of 3 or higher were considered to be a favorable outcome; for subjects with moderate-to-severe injury, a GOS-E of 5 or higher was considered to be a favorable outcome; for subjects with a moderate injury, a GOS-E of 7 or higher was considered to be a favorable outcome.
6 months post randomization
Secondary Outcomes (11)
Mortality
6 months
Disability Rating Scale
6 months
Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis
within 6 months
Potentially Associated Adverse Events: Pulmonary Embolism
within 6 months
Potentially Associated Adverse Events: Acute Ischemic Stroke
within 6 months
- +6 more secondary outcomes
Study Arms (2)
Progesterone
EXPERIMENTALFollowing a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (progesterone) will be administered as a continuous intravenous infusion at 0.5 mg/kg/hr for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table will be used by the on-sight pharmacy to mix the correct dose for a 10 cc/hour continuous infusion over the 72 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The progesterone will be combined with a 20% Intralipid mixture for infusion.
Placebo
PLACEBO COMPARATORPlacebo stock solution was the ethanol diluent required for dissolving progesterone. The volume of placebo to be mixed with intralipid was based on the same mg/kg/hr volume that would be required if PROG had been in the vial. Using an infusion pump through a dedicated IV line - a one hour "loading dose" of placebo plus intralipid was administered as a continuous intravenous infusion for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table was used by the on-sight pharmacy to mix the correct "dose" for a 10 cc/hour continuous infusion over the 72 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The placebo will be combined with a 20% Intralipid mixture for infusion.
Interventions
Following a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (progesterone or placebo) will be administered as a continuous intravenous infusion at 0.5 mg/kg/hr for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table will be used by the on-sight pharmacy to mix the correct dose for a 10 cc/hour continuous infusion over the 71 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The progesterone/placebo will be combined with a 20% Intralipid mixture for infusion.
Placebo stock solution is the ethanol diluent required for dissolving progesterone. The volume of placebo to be mixed with intralipid is based on the mg/kg/hr volume. Using an infusion pump through a dedicated IV line - a one hour "loading dose" of placebo plus intralipid is administered as a continuous intravenous infusion for 71 hours, then tapered over an additional 24 hours.
Eligibility Criteria
You may qualify if:
- Moderate to severe brain injury (GCS 12-4)
- Age 18 years or older
- Blunt, closed head injury
- Study drug initiated within 4 hours of injury
You may not qualify if:
- Non-Survivable injury
- Bilateral dilated unresponsive pupils
- Severe intoxication (ETOH \> 250 mg %)
- Spinal cord injury with neurological deficits
- Inability to perform activities of daily living prior to injury
- Cardiopulmonary arrest
- Status epilepticus on arrival
- Systolic blood pressure (SBP) \< 90 on arrival or for at least 5 minutes prior to enrollment
- O2 Sat \< 90 on arrival or for at least 5 minutes prior to enrollment
- Prisoner or ward of state
- Pregnant
- Active breast or reproductive organ cancers
- Known allergy to progesterone or intralipid components (egg yolk)
- Known history of clotting disorder
- Active thromboembolic event
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- David Wrightlead
- Medical University of South Carolinacollaborator
- Neurological Emergencies Treatment Trials Network (NETT)collaborator
Study Sites (36)
Maricopa Integrated Health System
Phoenix, Arizona, 85008, United States
Banner Good Samaritan
Phoenix, Arizona, United States
Scottsdale Healthcare
Scottsdale, Arizona, United States
University of Arizona Medical Center
Tuscon, Arizona, 85724, United States
Santa Clara Valley Hospital
Palo Alto, California, 94304, United States
Stanford Medical Center
Palo Alto, California, 94304, United States
San Francisco General Hospital
San Francisco, California, 94110, United States
Regional Medical Center-San Jose
San Jose, California, United States
Grady Memorial Hospital
Atlanta, Georgia, 30303, United States
University of Kentucky Medical Center
Lexington, Kentucky, 40536, United States
University of Maryland Shock Trauma
Baltimore, Maryland, 21201, United States
Detroit Receiving Hospital
Detroit, Michigan, 48202, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Sinai Grace Hospital
Detroit, Michigan, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
Beaumont Royal Oak Hospital
Royal Oak, Michigan, 48073, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55414, United States
North Memorial Hospital
Robbinsdale, Minnesota, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
St. Johns Mercy Medical Center
St Louis, Missouri, 63141, United States
Columbia New York Presbyterian Hospital
New York, New York, 10032, United States
University Hospital
Cincinnatti, Ohio, 45267, United States
Oregon Health Sciences University
Portland, Oregon, 97239, United States
St. Luke's Hospital
Bethlehem, Pennsylvania, 18017, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Hahnemann University Hospital
Philadelphia, Pennsylvania, 19102, United States
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson UniversityHospital
Philadelphia, Pennsylvania, 19107, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Regional Medical Center/Elvis Presley Memorial Trauma Center (The MED)
Memphis, Tennessee, United States
Austin/Brackenridge
Austin, Texas, 78752, United States
Memorial Hermann
Houston, Texas, 77030, United States
Brooke Army Medical Center
San Antonio, Texas, United States
Virginia Commonwealth
Richmond, Virginia, 23298, United States
Froedtert East Hospital
Milwaukee, Wisconsin, 53226, United States
Related Publications (2)
Zhao W, Pauls K. Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system. Clin Trials. 2016 Apr;13(2):223-33. doi: 10.1177/1740774515611889. Epub 2015 Oct 13.
PMID: 26464429DERIVEDWright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, Goldstein FC, Caveney AF, Howlett-Smith H, Bengelink EM, Manley GT, Merck LH, Janis LS, Barsan WG; NETT Investigators. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014 Dec 25;371(26):2457-66. doi: 10.1056/NEJMoa1404304. Epub 2014 Dec 10.
PMID: 25493974DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The trial was stopped early for futility with respect to the primary outcome.
Results Point of Contact
- Title
- David W. Wright, Associate Professor, Department of Emergency Medicine, Emory University
- Organization
- Emergency Neurosciences, Emergency Medicine, Emory University
Study Officials
- PRINCIPAL INVESTIGATOR
David W Wright, MD
Emory University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 14, 2009
First Posted
January 15, 2009
Study Start
March 1, 2010
Primary Completion
May 1, 2014
Study Completion
July 1, 2014
Last Updated
January 20, 2016
Results First Posted
July 3, 2015
Record last verified: 2015-12