Consciousness DisorderNCT05367999
A Clinical Decision Aid for Diagnosing Transient Loss of Consciousness
An observational study of Consciousness Disorder, run by Sheffield Teaching Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
BACKGROUND: Transient loss of consciousness (TLOC) - defined as spontaneous disruption of consciousness not due to head trauma and with complete recovery - has a lifetime prevalence of 50%. It is one of the commonest neurological complaints in primary and emergency care. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Consciousness Disorder
- What is being tested?
- initial Paroxysmal Event Profile
- How many people
- 186 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 9 Feb 2022to 30 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population will consist of screened admissions to the Emergency Department and Acute Medical Unit presenting with TLOC, as well as all new patients referred to the Neurology and Cardiology departments with TLOC.
Who may be able to join
- Patients first presenting with TLOC
- Referred to secondary care for diagnostic evaluation OR given firm diagnosis of syncope in accordance with European Society of Cardiology guidelines for syncope presentations not requiring further investigation
- Adult over the age of 16 years
- Able to complete iPEP questionnaire independently
- Participants do not need to be native English speaker but do need to have sufficient English language ability to complete iPEP without support
- Initial Exclusion Criteria:
Show all 13Show fewer
- Unable to give informed consent to participation in research
- Unable to complete iPEP independently
- Previous specialist (neurological or cardiological) assessment of TLOC
- Criteria for exclusion from analysis:
- No firm clinical diagnosis of TLOC (and its cause) at end of 6-month follow-up period
- Mixed diagnosis of multiple TLOC-causing disorders at end of 6-month follow-up; we exclude these participants from analysis as they would not have a single reference standard diagnosis, thus their inclusion in development may reduce model performance (since their questionnaire answers will describe multiple different kinds of episode), and in validation there is no principled way to assess performance of the prediction model if they have more than one reference diagnosis. A previous study of patients with suspected seizures in this population found that only 1.1% of patients could not be given a single aetiological diagnosis, so we do not anticipate this resulting in many exclusions.4
- Evidence of previous specialist (neurological or cardiological) assessment of TLOC.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Royal Hallamshire Hospital
Sheffield, South Yorkshire, S10 2JF
Northern General Hospital
Sheffield, South Yorkshire, S5 7AT
About this study
Official title: Development of a Clinical Decision Aid for the Differential Diagnosis of Transient Loss of Consciousness
BACKGROUND: Transient loss of consciousness (TLOC) - defined as spontaneous disruption of consciousness not due to head trauma and with complete recovery - has a lifetime prevalence of 50%. It is one of the commonest neurological complaints in primary and emergency care. Over 90% of TLOC is due to either syncope, epilepsy or dissociative seizures (DS, also known as 'Psychogenic Nonepileptic Seizures'). The rapid and accurate distinction of these diagnoses is vital to allow appropriate further management but at least 20-30% of patients are not managed optimally or misdiagnosed. We have previously demonstrated that, in patients with established diagnoses of epilepsy, syncope, or DS, an automated classifier using only information from 36 questions based on patient experience and lay witness reports (the initial Paroxysmal Event Profile, iPEP) could accurately diagnose 86.0% of patients (with 100% sensitivity and 91.7% specificity for syncope)
AIMS: To calibrate the iPEP for discrimination between syncope, epilepsy, and DS in patients newly presenting with TLOC, validate its performance in an independent sample, and to explore acceptability of the use of such a tool to people with TLOC and witnesses.
Read more
METHODS: Nested qualitative-quantitative prospective single-centre development and validation of the iPEP in patients presenting to Emergency Departments, syncope or epilepsy clinics with first presentations of TLOC, with semi-structured interviews conducted with a purposive sample of participants from the quantitative study. The iPEP will be calibrated using a previously-described procedure for variable selection and training of Random Forest (RF) classifiers, and validated with assessment of overall classification accuracy, alongside sensitivity, specificity, positive and negative predictive values, and area under receiver-operating curve for each of the three target diagnoses. Performance will be evaluated against a benchmark set by results from previous research in patients with established diagnoses of epilepsy, syncope, and DS.
OUTPUTS: Results will be submitted for publication in academic and professional literature. If performance from feasibility can be replicated in validation, the iPEP will be suitable to begin process of registration as a medical device for implementation in clinical pathways to minimise inappropriate referrals and treatment, streamline patient pathways, and enable earlier ordering of appropriate investigations to ensure prompt and appropriate diagnosis and management. If pilot performance could be replicated in this population and proportional savings from current estimated costs of misdiagnosis achieved, this could potentially save £63.9 million of annual UK healthcare expenditure.
- Conditions
- Consciousness Disorder
- Being tested
- initial Paroxysmal Event Profile
- Keywords
- TLOC, Seizures, Epilepsy, Syncope
- Medical subject headings
- Consciousness Disorders, Seizures, Epilepsy, Syncope
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
initial Paroxysmal Event ProfileDiagnostic test
The initial Paroxysmal Event Profile (iPEP) was derived from the paroxysmal event profile (PEP) and paroxysmal event observer (PEO) to provide a diagnostic tool aiming to differentiate between the most common underlying reasons for TLOC presentations: syncope, epilepsy, and dissociative seizures. The iPEP is a 35-item questionnaire developed from the PEP and PEO.5,25 The 5-point frequency scales used in response to each symptom in the PEP and PEO have been replaced with a binary 'present'/'not present' classification in recognition of the fact that the target patient group may have experienced only one or a few episodes of TLOC.
| Study group | Role | What they receive |
|---|---|---|
| Patients presenting with TLOC | A concurrent nested qualitative-quantitative design is used. Patients first presenting to an ED with TLOC (and witnesses) who have contributed to the quantitative part of this project will be offered participation in a qualitative interview study after completion of the iPEP during the initial study procedure. Capturing variation based on diagnosis, gender, age and participant/witness role, a purposive sample of participating participants and witnesses will be invited to semi-structured interviews in which they will be prompted to discuss their experiences of using the iPEP and their views on the accuracy in describing their peri-episodal experiences. Receives: Diagnostic Test: initial Paroxysmal Event Profile |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC for syncope
We will compare classifier-predicted diagnoses against final diagnoses obtained by expert consensus review of medical records. We will define performance in terms of AUC for cardiogenic syncope.
Measured: 6 months post-presentation
Secondary outcomes (1)
Overall classifier accuracy
We will compare classifier-predicted diagnoses against final diagnoses obtained by expert consensus review of medical records. We will define performance in terms of classifier accuracy, and sensitivity, specificity, positive and negative predictive values for other diagnoses (i.e., epileptic/dissociative seizures). This will enable direct comparison with current rates of misdiagnosis.
Measured: 6 months post-presentation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2022
- Study start9 Feb 2022
- Primary completion30 Jun 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Consciousness DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Markus Reuber, Principal investigator, Honorary Consultant NeurologistAlistair Wardrope, Principal investigator, Specialty Registrar in Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05367999
- Sponsor's protocol ID
- STH20060
- Status last verified
- Jan 2024
- First submitted
- 19 Apr 2022
- Last updated
- 3 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Clinical Decision Aid for the Differential Diagnosis of Transient Loss of Consciousness
- ClinicalTrials.gov ID
- NCT05367999
- Acronym / sponsor ID
- STH20060
- Conditions
- Consciousness Disorder
- Keywords
- TLOC, Seizures, Epilepsy, Syncope
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- 9 Feb 2022 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 10 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
BACKGROUND: Transient loss of consciousness (TLOC) - defined as spontaneous disruption of consciousness not due to head trauma and with complete recovery - has a lifetime prevalence of 50%. It is one of the commonest neurological complaints in primary and emergency care. Over 90% of TLOC is due to either syncope, epilepsy or dissociative seizures (DS, also known as 'Psychogenic Nonepileptic Seizures'). The rapid and accurate distinction of these diagnoses is vital to allow appropriate further management but at least 20-30% of patients are not managed optimally or misdiagnosed. We have previously demonstrated that, in patients with established diagnoses of epilepsy, syncope, or DS, an automated classifier using only information from 36 questions based on patient experience and lay witness reports (the initial Paroxysmal Event Profile, iPEP) could accurately diagnose 86.0% of patients (with 100% sensitivity and 91.7% specificity for syncope)
AIMS: To calibrate the iPEP for discrimination between syncope, epilepsy, and DS in patients newly presenting with TLOC, validate its performance in an independent sample, and to explore acceptability of the use of such a tool to people with TLOC and witnesses.
METHODS: Nested qualitative-quantitative prospective single-centre development and validation of the iPEP in patients presenting to Emergency Departments, syncope or epilepsy clinics with first presentations of TLOC, with semi-structured interviews conducted with a purposive sample of participants from the quantitative study. The iPEP will be calibrated using a previously-described procedure for variable selection and training of Random Forest (RF) classifiers, and validated with assessment of overall classification accuracy, alongside sensitivity, specificity, positive and negative predictive values, and area under receiver-operating curve for each of the three target diagnoses. Performance will be evaluated against a benchmark set by results from previous research in patients with established diagnoses of epilepsy, syncope, and DS.
OUTPUTS: Results will be submitted for publication in academic and professional literature. If performance from feasibility can be replicated in validation, the iPEP will be suitable to begin process of registration as a medical device for implementation in clinical pathways to minimise inappropriate referrals and treatment, streamline patient pathways, and enable earlier ordering of appropriate investigations to ensure prompt and appropriate diagnosis and management. If pilot performance could be replicated in this population and proportional savings from current estimated costs of misdiagnosis achieved, this could potentially save £63.9 million of annual UK healthcare expenditure.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients presenting with TLOC | – | Diagnostic Test: initial Paroxysmal Event ProfileA concurrent nested qualitative-quantitative design is used. Patients first presenting to an ED with TLOC (and witnesses) who have contributed to the quantitative part of this project will be offered participation in a qualitative interview study after completion of the iPEP during the initial study procedure. Capturing variation based on diagnosis, gender, age and participant/witness role, a purposive sample of participating participants and witnesses will be invited to semi-structured interviews in which they will be prompted to discuss their experiences of using the iPEP and their views on the accuracy in describing their peri-episodal experiences. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population will consist of screened admissions to the Emergency Department and Acute Medical Unit presenting with TLOC, as well as all new patients referred to the Neurology and Cardiology departments with TLOC.
Key inclusion criteria (13 listed)
- Patients first presenting with TLOC
- Referred to secondary care for diagnostic evaluation OR given firm diagnosis of syncope in accordance with European Society of Cardiology guidelines for syncope presentations not requiring further investigation
- Adult over the age of 16 years
- Able to complete iPEP questionnaire independently
- Participants do not need to be native English speaker but do need to have sufficient English language ability to complete iPEP without support
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| initial Paroxysmal Event ProfileThe initial Paroxysmal Event Profile (iPEP) was derived from the paroxysmal event profile (PEP) and paroxysmal event observer (PEO) to provide a diagnostic tool aiming to differentiate between the most common underlying reasons for TLOC presentations: syncope, epilepsy, and dissociative seizures. The iPEP is a 35-item questionnaire developed from the PEP and PEO.5,25 The 5-point frequency scales used in response to each symptom in the PEP and PEO have been replaced with a binary 'present'/'not present' classification in recognition of the fact that the target patient group may have experienced only one or a few episodes of TLOC. | Diagnostic test | Patients presenting with TLOC |
Primary outcome
AUC for syncope
Time frame: 6 months post-presentation
We will compare classifier-predicted diagnoses against final diagnoses obtained by expert consensus review of medical records. We will define performance in terms of AUC for cardiogenic syncope.
1 secondary outcome
Overall classifier accuracy
Time frame: 6 months post-presentation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Reuber principal investigator
Honorary Consultant Neurologist
Alistair Wardrope principal investigator
Specialty Registrar in Neurology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Consciousness Disorder, run by Sheffield Teaching Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC for syncope (time frame: 6 months post-presentation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2024.