Study for the Improvement of Long-Term Outcome Prediction in Patients in Coma After Cardiac Arrest

NCT ID: NCT02231060

Last Updated: 2018-12-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2018-12-06

Brief Summary

The primary objective of HOPE is to improve the accuracy of outcome prediction in anoxic-ischemic encephalopathy following cardiac arrest by bringing under close scrutiny some of the existing methods used for this purpose (e.g. somato-sensory evoked potentials). HOPE is the first multicenter prospective cohort study on coma prognosis to control for the effect of a possible self-fulfilling prophecy at the ICU and to cover the acute and neurorehabilitation phases with a long-term follow-up longer than the usual three or six months.

Detailed Description

HOPE conducts a 2.5-year multicenter prospective cohort study in Germany on outcome prediction in the early stages of coma caused by cerebral hypoxia-ischemia.

The main features of the project are:

• Control for a self-fulfilling prophecy
• Long-term follow-up (12 months) covering acute and neurorehabilitation phases
• Use of sensitive measures of level of consciousness
• Further in-depth and systematic examination of the predictive value of somato-sensory evoked potentials (SSEP)

Using as a reference existing guidelines and previous research, we consider the following factors to be predictors of a negative outcome with a high specificity of > 90% with small 95% confidence intervals: loss of cortical N20 SEP potentials, loss of more than one brain stem reflex, non-reactive EEG, or a NSE above 33 mcg/L. We refer to the presence of any of these specific unfavourable test results during the ICU treatment as a "negative predictor". Therefore, our null hypothesis is that the probability of a favourable outcome, despite the presence of a negative predictor, is < 10%. We will use Simon's two-stage design. The null hypothesis will be tested against a one-sided alternative. In the first stage, we will accrue 72 patients. If there are 8 or fewer good outcomes in these 72 patients, the study will be discontinued because the null hypothesis could not be rejected. Otherwise, we will recruit 100 additional patients to gather a total of 172. The null hypothesis will be rejected if 28 or more favourable outcomes are observed in these 172 patients. This design yields a type I error rate of 0.05 and power of 80% if the true response rate is 25%, i.e. if indeed 25% or more patients have a favourable outcome despite a negative predictor. This calculation is based on the assumption that 25% of the enrolled patients have at least one negative predictor.

HOPE has seven data entry points (i.e. study visits).The primary endpoints are completion of the follow-up period or patient death. HOPE collects clinical and demographic data in accordance to Utstein-style recommendations. The most crucial part of the study is determining the current level of consciousness by means of the revised version of the Coma Recovery Scale (CRS-R). The CRS-R allows a precise categorization of the current level of consciousness based on a structured and systematic clinical examination of auditory, visual, motor, oromotor, communication and arousal functions. Other assessment instruments employed yield information about functional outcome/ADL, neuropsychological performance, and health-related quality of life.

Study centers will collect data prospectively following a data acquisition timeline (e.g. t0 to t6). Visits t0 to t2 will take place at acute-setting ICUs; visits t3 to t5 at neurorehabilitation centers; and visit t6 at the patients' location of residence 12 months after day 0. A manual and data dictionary will be provided to all centres along with the case report forms (CRF). All study centers will send pseudonymized data weekly by certified mail to the Central Study Centre (CSC) located at the Department of Neurology of the University of Munich. All study centres, including the CSC, will check the data for completeness, plausibility, accuracy, consistency and outliers. Legal representatives of coma patients, who decline to participate, will be asked to provide data on socio-demographic variables and reason for declining. The CSC will store the data at a database and will be responsible for safeguarding and analysing it. Patients/Legal representatives will be asked to remain in the study for a further follow-up. After completion of the follow-up period, datasets will be irreversibly anonymised.

We will analyze the positive predictive value of a dichotomous prognostic marker (favorable or unfavourable SSEP). For this purpose, we will use two definitions of favorable outcome, i.e. a functional and a behavioral one. If outcome is defined with respect to independence in daily life, we will use a modified Rankin Scale score of 0-3 (no symptoms - moderate disability, but able to walk independently) to categorize a favorable functional outcome. In the context of a catastrophic event such as cardiac arrest with high likelihood of permanent VS, it is our experience that some patients and families consider regaining functional communications skills also a favourable outcome. In a separate analysis, we will therefore use the recovery of full consciousness as measured by the CRS-R to define a favorable behavioral outcome. To analyse the effect of covariates on functional and behavioral outcomes, we will use mixed effects regression models, including both fixed and random effects. This method of analyzing longitudinal data is highly effective to examine change trajectories with several unequally spaced waves of data. Covariates will be sociodemographic variables, prognostic variables and treatment factors (e.g. use of therapeutic hypothermia), adjusted for age and sex.

Conditions

Anoxic-Ischemic Encephalopathy

Keywords

Outcome Prediction; Anoxic-Ischemic Encephalopathy; Coma; Vegetative State; Minimally Conscious State; Chronic Disorders of Consciousness

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

AIE after Cardiac Arrest

Male and female patients with AIE following CA.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 85 years
• Cause of admission to ICU: cardiac arrest (in or out of hospital)
• Glasgow-Coma-Scale < 9 at time of study enrolment (3 to 8 days after cardiac arrest)
• Informed consent signed by legal guardian/next-of-kin

Exclusion Criteria

• Stroke (as it may interfere with SSEP testing)
• Pre-existing coma/vegetative state/minimally conscious state
• Terminal malignant disease
• Survival in the next 12 months extremely unlikely
• Existing advanced directive that demands cessation of therapy/life support
• Palliative care/withdrawal of life support during treatment at the ICU
• Barbiturate-induced general anesthesia during the first 3 days after cardiac arrest
• Impossibility of assessing current level of consciousness with the Glasgow Coma Scale due to a long-term deep sedation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Else Kröner Fresenius Foundation

OTHER

Sponsor Role: collaborator

University Hospital Augsburg

OTHER

Sponsor Role: collaborator

Klinikum Ingolstadt

OTHER

Sponsor Role: collaborator

Klinikum Rosenheim

OTHER

Sponsor Role: collaborator

Therapiezentrum Burgau

OTHER

Sponsor Role: collaborator

Schoen Clinic Bad Aibling

OTHER

Sponsor Role: collaborator

Schön Klinik München Schwabing

UNKNOWN

Sponsor Role: collaborator

Asklepios Stadtklinik Bad Tölz

UNKNOWN

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: collaborator

Krankenhaus Barmherzige Brüder München

UNKNOWN

Sponsor Role: collaborator

Roteskreuzklinikum München

UNKNOWN

Sponsor Role: collaborator

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Andreas Bender

Professor, Doctor Medicinae (Prof. Dr. med.)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andreas Bender, MD

Role: PRINCIPAL_INVESTIGATOR

Ludwig-Maximilians-Universität München

Locations

Department of Neurology, Klinikum Augsburg

Augsburg, Bavaria, Germany

I. Medizinische Klinik, Klinikum Augsburg

Augsburg, Bavaria, Germany

Schön Klinik Bad Aibling

Bad Aibling, Bavaria, Germany

Dept of Neurology, Asklepios Stadtklinik Bad Tölz

Bad Tölz, Bavaria, Germany

Therapiezentrum Burgau

Burgau, Bavaria, Germany

Medizinische Klinik I und IV, Klinikum Ingolstadt

Ingolstadt, Bavaria, Germany

Neurologische Klinik, Klinikum Ingolstadt

Ingolstadt, Bavaria, Germany

Deutsches Herzzentrum Muenchen

Munich, Bavaria, Germany

Krankenhaus Barmherzige Brüder München

Munich, Bavaria, Germany

Schön Klinik München Schwabing

Munich, Bavaria, Germany

Department of Neurology, University of Munich

Munich, Bavaria, Germany

Internal ICU, Medical Clinic and Polyclinic IV, University of Munich

Munich, Bavaria, Germany

Medizinische Klinik und Poliklinik I, University of Munich

Munich, Bavaria, Germany

Department of Neurology

Munich, Bavaria, Germany

Clinic for Anesthesiology, University of Munich

Munich, Bavaria, Germany

Neurologische Klinik, RoMed Klinikum Rosenheim

Rosenheim, Bavaria, Germany

Countries

Germany

References

Lopez-Rolon A, Bender A; Project HOPE Investigator Group. Hypoxia and Outcome Prediction in Early-Stage Coma (Project HOPE): an observational prospective cohort study. BMC Neurol. 2015 May 15;15:82. doi: 10.1186/s12883-015-0337-x.

Reference Type: BACKGROUND

PMID: 25971341 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451883/

Hypoxia and Outcome Prediction in Early-Stage Coma (Project HOPE): an observational prospective cohort study

Other Identifiers

2014_A55

Identifier Type: -

Identifier Source: org_study_id