Progesterone for the Treatment of Traumatic Brain Injury III

NCT ID: NCT00822900

Last Updated: 2016-01-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

882 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2014-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Progesterone

Following 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.

Group Type EXPERIMENTAL

Progesterone

Intervention Type DRUG

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

Placebo 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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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Progesterone

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Concern for inability to follow up at 6 months
* Anyone listed in the Opt out registry
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of South Carolina

OTHER

Sponsor Role collaborator

Neurological Emergencies Treatment Trials Network (NETT)

NETWORK

Sponsor Role collaborator

David Wright

OTHER

Sponsor Role lead

Responsible Party

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David Wright

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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David W Wright, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Maricopa Integrated Health System

Phoenix, Arizona, United States

Site Status

Banner Good Samaritan

Phoenix, Arizona, United States

Site Status

Scottsdale Healthcare

Scottsdale, Arizona, United States

Site Status

University of Arizona Medical Center

Tuscon, Arizona, United States

Site Status

Santa Clara Valley Hospital

Palo Alto, California, United States

Site Status

Stanford Medical Center

Palo Alto, California, United States

Site Status

San Francisco General Hospital

San Francisco, California, United States

Site Status

Regional Medical Center-San Jose

San Jose, California, United States

Site Status

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

University of Kentucky Medical Center

Lexington, Kentucky, United States

Site Status

University of Maryland Shock Trauma

Baltimore, Maryland, United States

Site Status

Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Sinai Grace Hospital

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Beaumont Royal Oak Hospital

Royal Oak, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

North Memorial Hospital

Robbinsdale, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

St. Johns Mercy Medical Center

St Louis, Missouri, United States

Site Status

Columbia New York Presbyterian Hospital

New York, New York, United States

Site Status

University Hospital

Cincinnatti, Ohio, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

St. Luke's Hospital

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson UniversityHospital

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Regional Medical Center/Elvis Presley Memorial Trauma Center (The MED)

Memphis, Tennessee, United States

Site Status

Austin/Brackenridge

Austin, Texas, United States

Site Status

Memorial Hermann

Houston, Texas, United States

Site Status

Brooke Army Medical Center

San Antonio, Texas, United States

Site Status

Virginia Commonwealth

Richmond, Virginia, United States

Site Status

Froedtert East Hospital

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 26464429 (View on PubMed)

Wright 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.

Reference Type DERIVED
PMID: 25493974 (View on PubMed)

Other Identifiers

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1RO1 NS062778-01

Identifier Type: -

Identifier Source: secondary_id

IRB00014409

Identifier Type: -

Identifier Source: org_study_id

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