Progesterone for the Treatment of Traumatic Brain Injury III (ProTECT)

This study has been terminated.
(futility: low conditional power to demonstrate benefit of progesterone)
Sponsor:
Collaborators:
Medical University of South Carolina
Neurological Emergencies Treatment Trials Network (NETT)
Information provided by (Responsible Party):
David Wright, Emory University
ClinicalTrials.gov Identifier:
NCT00822900
First received: January 14, 2009
Last updated: January 14, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Traumatic Brain Injury
Drug: Progesterone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Favorable outcome as determined by the Glasgow Outcome Scale-Extended (GOSE) [ Time Frame: 6 months post randomization ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Disability Rating Scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.

  • Potentially Associated Adverse Events: Myocardial infarction [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Pulmonary embolism [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Acute ischemic stroke [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Deep venous thrombosis [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Unexplained increased liver-enzyme level [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Sepsis [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Pneumonia [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Central nervous system infection [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment

  • Potentially Associated Adverse Events: Phlebitis or thrombophlebitis [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    adverse event prespecified as potentially associated with treatment


Enrollment: 882
Study Start Date: March 2010
Study Completion Date: July 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Placebo Comparator: Placebo
Following a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00822900

  Show 36 Study Locations
Sponsors and Collaborators
David Wright
Medical University of South Carolina
Neurological Emergencies Treatment Trials Network (NETT)
Investigators
Principal Investigator: David W Wright, MD Emory University
  More Information

Additional Information:
No publications provided by Emory University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Wright, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT00822900     History of Changes
Other Study ID Numbers: IRB00014409, 1RO1 NS062778-01
Study First Received: January 14, 2009
Last Updated: January 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Trauma
Brain Injury

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Progesterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins

ClinicalTrials.gov processed this record on April 27, 2015