Long Term Effects of Erythropoietin in Patients With Moderate to Severe Traumatic Brain Injury

Long Term Effects of Erythropoietin in Patients With Moderate to Severe Traumatic Brain Injury A Follow-up Study of an International Randomised Controlled Trial

Traumatic brain injury is catastrophic event that commonly require treatment in an intensive care unit. Management is mainly supportive aiming at avoiding hypoxia, hypotension, hypoglycaemia and increased intracerebral pressure. Thus far efforts to find a specific pharmacologic therapies have been disappointing. Recently it was demonstrated that recombinant erythropoietin has been found to decrease mortality at six months from injury but without significantly improving functional neurological outcome (GOSe). Whether this survival benefit of EPO is sustained beyond 6 months is unknown.

In the current study survival data will be collected centrally and patients alive or person responsible will be invited to participate in an evaluation of neurological function and quality of life. Factors associated with time to death as well as factors associated with long term quality of life will be determined with statistical methods.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: erythropoietin; Drug: Placebos

Detailed Description

Aim: In this post hoc study of a RCT the primary aim is to determine the effect of EPO compared to placebo in improving outcome, including survival, neurological function and quality of life two years after the conclusion of the EPO-TBI study (two to seven years after moderate or severe TBI occurring in individual patients).

Design: A long term follow-up study of a prospective, multi-centre, double blind, phase III, randomised controlled trial.

Methods: Survival status at the time when this follow-up trial is executed will obtained in all patients. Time from injury will vary between 2 to 7 years depending on when the patient was enrolled. This information will obtained from hospital notes, national register offices and/or national statistical bureaus. Since the trial was an international RCT, strategies may vary and will take into account local circumstances. Local plans will be developed by the local principal investigators and approved by the management committee.

Data includes

• Survival status at long term follow up (alive/dead)
• Time from injury to assessment (days)
• If the patients is deceased, time of death and time from injury in days

Quality of life assessment

Patients (or a proxy - generally a close family member) who are alive at 2-7 years after randomisation will be interviewed by trained assessors. The same contact person as used in the primary trial will be contacted primarily. Consent will be obtained for the conduction for long term assessment. Assessors will use a standardized structured telephone questionnaires to determine GOSE and QOL. Neurological outcomes will then be defined as favourable (GOSE 5 to 8; moderate disability and good recovery) or unfavourable (GOSE 1 to 4; death and severe disability). Data include:

• Time of assessment
• Time from injury in days
• Follow-up GOSE
• Follow-up EQ-5D
• Follow-up SF-12

• Study Type: Observational
• Enrollment (Actual): 356

Contacts and Locations

• Study Contact: Name: Markus B Skrifvars; Phone Number: +61399030343; Email: markus.skrifvars@monash.edu
• Study Contact Backup: Name: Lorraine Little; Phone Number: +61399030513; Email: lorraine.little@monash.edu

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Australian and New Zealand Intensive Care Research Centre, Monash University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The EPO-TBI study conducted between 2010 and 2015 enrolled a total of 606 patients treated for moderate to severe traumatic brain injury in the intensive care unit. Of these consent was withdrawn in 3 patients. Of the 603 patients, 524 we alive at 6 months. Survival status will be checked in these 524 patients and those alive will be included in a follow-up of functional recover and quality of life.

Description

Inclusion Criteria:

• Participation in the EPO-TBI study without withdrawal of informed consent.

Exclusion criteria:

• Failure to to consent for the conduction of the follow-up assessment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Erythropoietin; Patients were treated with EPO during the EPO-TBI study in 2010-2014.	Drug: erythropoietin; Patients were given erythropoietin during the EPO-TBI study in 2010-2014. In the current follow-up we will evaluate any possible long term differences between patients treated with etrythropoietin compared to placebo.; Other Names: EPOETIN ALFA
Placebo; Patients were treated with placebo during the EPO-TBI study in 2010-2014.	Drug: Placebos; Patients were given placebo during the EPO-TBI study in 2010-2014. In the current follow-up we will evaluate any possible long term differences between patients treated with etrythropoietin compared to placebo.; Other Names: Sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality and time to mortality at least 2 years from injury	Survival status with time to death in those deceased	2-7 years from injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow outcome scale extended	Neurological outcome	2-7 years from injury
SF-12	Quality of life scale	2-7 years from injury
EQ-5D	Quality of life scale	2-7 years from injury

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Collaborators: Monash University
• Investigators: Principal Investigator: Rinaldo Bellomo, ANZIC-RC Monash University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 19, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 1, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: erythropoietin; traumatic brain injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Hematinics; Epoetin Alfa
• Other Study ID Numbers: ANZIC-RC EPO-TBI Long term

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No