Head PainCoHeadNCT01174901
Copeptin for Risk Stratification in Non-traumatic Headache in the Emergency Setting - The CoHead Study
An observational study of Head Pain, run by University Hospital, Basel, Switzerland at 2 sites in Switzerland.
Trial summary
Headache is a common symptom, and patients often seek medical attention at emergency departments due to headaches. The aim of the CoHead Study is to find out if it is possible by measuring copeptin, a marker of stress in the blood, to find out which patients have simple headaches and which patients have dangerous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head Pain
- How many people
- 400 participants
- Where
- 2 sitesSwitzerland
- Study dates
- Oct 2010to Aug 2013
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients presenting to emergency department or walk-in clinic
Who may be able to join
- headache at the time of screening
- Patients must be able to give informed consent
Who cannot join
- less than 18 years of age
- preceding (head) trauma
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
Kantonsspital Aarau AG
Aarau, Canton of Aargau, 5001
University Hospital of Basel
Basel, Canton of Basel-City, 4031
About this study
Headache is a common symptom, and patients often seek medical attention at emergency departments due to headaches.
The aim of the CoHead Study is to find out if it is possible by measuring copeptin, a marker of stress in the blood, to find out which patients have simple headaches and which patients have dangerous headaches that are the symptom of an underlying disease and need further investigation and treatment.
Read more
Copeptin is a marker for physical stress and has been tested in patients with stroke, heart attack and pneumonia. In all these illnesses, the patients with the most serious forms had the highest levels of copeptin, while the ones with only mild presentation or no affection at all had the lowest levels of copeptin.
The investigators expect to show the same in patients with headaches.
Read the detailed description
Background: In the emergency setting, non-traumatic headache (NTH) is in 80% a benign symptom, but serious causes have to be ruled out.
Copeptin, as a surrogate marker for antidiuretic hormone (ADH), is a marker for the individual stress level, even more subtle than cortisol. As a prognostic stress hormone it holds promise as a prognostic point of care tool in the risk stratification of different acute illnesses such as acute myocardial infarction, respiratory tract infections and cerebrovascular events, among others.
Objective: To evaluate copeptin as a marker for risk stratification in NTH. Design: Prospective multicenter observational cohort study with a derivation set and a validation set.
Location Setting: Emergency Department (ED) and Medical Policlinic (MUP; walk-in clinic) and Neurologic Clinic (NC) of the University Hospital of Basel. ED and NC of the Cantonal Hospital of Aarau.
Intervention: Patients presenting to the ED or the MUP or the NC with NTH are recruited during a 1-year-period. After informed consent is given by the patient, baseline data will be assessed including medical history, clinical items (i.e. neurological status, vital parameters, blood pressure, BMI) and routine laboratory items. Patients will be evaluated using a validated standardized diagnostic tool and questionnaire. CT scans and other diagnostics, such as lumbar puncture, MRI, etc., will be ordered upon request of the treating physician. All diagnostic procedures, results, diagnosis made by the treating physicians and initiated therapy will be recorded. Copeptin will be measured on admission by batch analysis by blinded laboratory staff upon completion of the study.
After 3 months, all patients will be followed-up by a structured telephone interview to assess the final diagnosis and outcome (i.e. MIDAS-Questionnaire). The final diagnosis will be made by two independent physicians according to ICHDII-criteria and verified by a board-certified neurologist, all blinded to copeptin levels. Thereby, primary and secondary headache entities will be classified according to ICHD.
Endpoints: The primary endpoint of this study is serious secondary NTH as opposed to benign, self-limiting NTH. Serious secondary NTH will be defined as a composite endpoint including different secondary NTH causes and entities as listed in the International Classification of Headache Disorders (ICHD)-II-Criteria.
The secondary endpoint will be clinical outcome of patients; thereby we will look at all-cause mortality within the 3-month follow-up period and at morbidity measured by the MIDAS-questionnaire.
Study hypothesis: We hypothesize that copeptin will serve as a point of care tool to discriminate benign headache from potentially serious secondary headaches (e.g. subarachnoidal hemorrhage (SAH) or cerebral aneurysm, intracranial bleeding (ICB), brain tumor, vasculitis, meningitis) which require prompt hospitalisation and intervention. Based on copeptin values measured in other acute diseases, we assume a critical range between 5 and 20 pmol/l. The lower copeptin cutoff point of ≤ 5 pmol/l will have a sensitivity of ≥ 97% for ruling out serious secondary headache, and the higher cutoff point of ≥ 20 pmol/l will have a specificity of 90% to confirm serious NTH.
Analysis: Based on data of two previous years, we aim to recruit 600 - 800 patients within one year at the sites of Basel and Aarau, respectively, of which 10-20% will present with serious secondary NTH. We will calculate 95% confidence intervals of sensitivity of copeptin of <10% and perform multivariable logistic regression analysis to assess the independent and additive utility of copeptin compared with other risk scores and outcome predictors. The first 50% of patients will be used as derivation set and the second 50% as the validation set, based on the timely inclusion of patients.
Significance: If copeptin as a biomarker safely rules out serious secondary causes of NTH, it will represent a tool for an optimized allocation of health care resources.
- Conditions
- Head Pain
- Keywords
- cephalalgia, copeptins, biomarkers, headache, C-terminal provasopression, physiological stress response
- Medical subject headings
- Headache
What is being measured
The primary outcome is the main question the study is designed to answer.
Differentiation between serious secondary non-traumatic headache as opposed to benign, self-limiting non-traumatic headache by copeptin level measurement
Assessment of the prognostic value of copeptin to predict the primary endpoint (serious secondary NTH).
Non-traumatic headache (NTH) will be assessed and defined according to the ICHD-II-Criteria. Serious secondary NTH will be defined as a composite endpoint including different secondary NTH causes and entities as listed in the ICHD-II-Criteria.
Measured: At study entry, assessment of baseline characteristics, questionnaire, further investigations done by attending physician, and blood collection for copeptin measurement. telephone interview after 3 months.
Secondary outcomes (3)
clinical outcome of patients
- all-cause mortality within the 3-month follow-up period
- morbidity measured by the MIDAS-questionnaire which is performed at study entry and at the 3-month-interview
Measured: study entry and 3-month-interview
Additive benefit on sensitivity if copeptin and a diagnostic algorithm are combined
A validated, diagnostic algorithm consisting of four clinical scenarios (published by Grimaldi et al.) will be used by the study team upon entry into the study. We will evaluate the additive benefit of copeptin to this algorithm with means of multivariate logistic regression analysis and calculation of reclassification tables.
Measured: study entry and 3-month-interview
Comparison of copeptin with other potential biomarkers in non-traumatic headache
We will compare the diagnostic and prognostic accuracy of copeptin with other potential biomarkers which have been reported to be of diagnostic value in migraine or cerebrovascular events, both being potential clinical scenarios of non-traumatic headache.
Measured: study entry and 3-month-interview
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2010 (estimated)
- Study startOct 2010
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Head PainStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, MD, PhD, Principal investigator, Department of Endocrinology, University Hospital of Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01174901
- Sponsor's protocol ID
- CoHead
- Acronym
- CoHead
- Status last verified
- May 2014
- First submitted
- 2 Aug 2010
- Last updated
- 26 May 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, Bingisser R, Muller K, Meckel S, Gass A, Kappos L, Steck AJ, Engelter ST, Muller B, Christ-Crain M. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann Neurol. 2009 Dec;66(6):799-808. doi: 10.1002/ana.21783.
PubMed 20035506Katan M, Muller B, Christ-Crain M. Copeptin: a new and promising diagnostic and prognostic marker. Crit Care. 2008;12(2):117. doi: 10.1186/cc6799. Epub 2008 Mar 6.
PubMed 18355399Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, Bergmann A, Potocki M, Noveanu M, Breidthardt T, Christ A, Boldanova T, Merki R, Schaub N, Bingisser R, Christ M, Mueller C. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009 Jun 30;54(1):60-8. doi: 10.1016/j.jacc.2009.01.076.
PubMed 19555842Friedman BW, Hochberg ML, Esses D, Grosberg B, Corbo J, Toosi B, Meyer RH, Bijur PE, Lipton RB, Gallagher EJ. Applying the International Classification of Headache Disorders to the emergency department: an assessment of reproducibility and the frequency with which a unique diagnosis can be assigned to every acute headache presentation. Ann Emerg Med. 2007 Apr;49(4):409-19, 419.e1-9. doi: 10.1016/j.annemergmed.2006.11.004. Epub 2007 Jan 8.
PubMed 17210203Grimaldi D, Cevoli S, Cortelli P. Headache in the emergency department. How to handle the problem? Neurol Sci. 2008 May;29 Suppl 1:S103-6. doi: 10.1007/s10072-008-0899-0.
PubMed 18545909Blum CA, Winzeler B, Nigro N, Schuetz P, Biethahn S, Kahles T, Mueller C, Timper K, Haaf K, Tepperberg J, Amort M, Huber A, Bingisser R, Sandor PS, Nedeltchev K, Muller B, Katan M, Christ-Crain M. Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study. J Headache Pain. 2017 Dec;18(1):21. doi: 10.1186/s10194-017-0733-2. Epub 2017 Feb 13.
PubMed 28197843
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Copeptin for Risk Stratification in Non-traumatic Headache in the Emergency Setting - The CoHead Study
- ClinicalTrials.gov ID
- NCT01174901
- Acronym / sponsor ID
- CoHead / CoHead
- Conditions
- Head Pain
- Keywords
- cephalalgia, copeptins, biomarkers, headache, C-terminal provasopression, physiological stress response
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 4 Aug 2010 (estimated)
- 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.
Headache is a common symptom, and patients often seek medical attention at emergency departments due to headaches.
The aim of the CoHead Study is to find out if it is possible by measuring copeptin, a marker of stress in the blood, to find out which patients have simple headaches and which patients have dangerous headaches that are the symptom of an underlying disease and need further investigation and treatment.
Copeptin is a marker for physical stress and has been tested in patients with stroke, heart attack and pneumonia. In all these illnesses, the patients with the most serious forms had the highest levels of copeptin, while the ones with only mild presentation or no affection at all had the lowest levels of copeptin.
The investigators expect to show the same in patients with headaches.
Detailed description
Background: In the emergency setting, non-traumatic headache (NTH) is in 80% a benign symptom, but serious causes have to be ruled out.
Copeptin, as a surrogate marker for antidiuretic hormone (ADH), is a marker for the individual stress level, even more subtle than cortisol. As a prognostic stress hormone it holds promise as a prognostic point of care tool in the risk stratification of different acute illnesses such as acute myocardial infarction, respiratory tract infections and cerebrovascular events, among others.
Objective: To evaluate copeptin as a marker for risk stratification in NTH. Design: Prospective multicenter observational cohort study with a derivation set and a validation set.
Location Setting: Emergency Department (ED) and Medical Policlinic (MUP; walk-in clinic) and Neurologic Clinic (NC) of the University Hospital of Basel. ED and NC of the Cantonal Hospital of Aarau.
Intervention: Patients presenting to the ED or the MUP or the NC with NTH are recruited during a 1-year-period. After informed consent is given by the patient, baseline data will be assessed including medical history, clinical items (i.e. neurological status, vital parameters, blood pressure, BMI) and routine laboratory items. Patients will be evaluated using a validated standardized diagnostic tool and questionnaire. CT scans and other diagnostics, such as lumbar puncture, MRI, etc., will be ordered upon request of the treating physician. All diagnostic procedures, results, diagnosis made by the treating physicians and initiated therapy will be recorded. Copeptin will be measured on admission by batch analysis by blinded laboratory staff upon completion of the study.
After 3 months, all patients will be followed-up by a structured telephone interview to assess the final diagnosis and outcome (i.e. MIDAS-Questionnaire). The final diagnosis will be made by two independent physicians according to ICHDII-criteria and verified by a board-certified neurologist, all blinded to copeptin levels. Thereby, primary and secondary headache entities will be classified according to ICHD.
Endpoints: The primary endpoint of this study is serious secondary NTH as opposed to benign, self-limiting NTH. Serious secondary NTH will be defined as a composite endpoint including different secondary NTH causes and entities as listed in the International Classification of Headache Disorders (ICHD)-II-Criteria.
The secondary endpoint will be clinical outcome of patients; thereby we will look at all-cause mortality within the 3-month follow-up period and at morbidity measured by the MIDAS-questionnaire.
Study hypothesis: We hypothesize that copeptin will serve as a point of care tool to discriminate benign headache from potentially serious secondary headaches (e.g. subarachnoidal hemorrhage (SAH) or cerebral aneurysm, intracranial bleeding (ICB), brain tumor, vasculitis, meningitis) which require prompt hospitalisation and intervention. Based on copeptin values measured in other acute diseases, we assume a critical range between 5 and 20 pmol/l. The lower copeptin cutoff point of ≤ 5 pmol/l will have a sensitivity of ≥ 97% for ruling out serious secondary headache, and the higher cutoff point of ≥ 20 pmol/l will have a specificity of 90% to confirm serious NTH.
Analysis: Based on data of two previous years, we aim to recruit 600 - 800 patients within one year at the sites of Basel and Aarau, respectively, of which 10-20% will present with serious secondary NTH. We will calculate 95% confidence intervals of sensitivity of copeptin of <10% and perform multivariable logistic regression analysis to assess the independent and additive utility of copeptin compared with other risk scores and outcome predictors. The first 50% of patients will be used as derivation set and the second 50% as the validation set, based on the timely inclusion of patients.
Significance: If copeptin as a biomarker safely rules out serious secondary causes of NTH, it will represent a tool for an optimized allocation of health care resources.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients presenting to emergency department or walk-in clinic
Key inclusion criteria (2 listed)
- headache at the time of screening
- Patients must be able to give informed consent
Key exclusion criteria (2 listed)
- less than 18 years of age
- preceding (head) trauma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Differentiation between serious secondary non-traumatic headache as opposed to benign, self-limiting non-traumatic headache by copeptin level measurement
Time frame: At study entry, assessment of baseline characteristics, questionnaire, further investigations done by attending physician, and blood collection for copeptin measurement. telephone interview after 3 months.
Assessment of the prognostic value of copeptin to predict the primary endpoint (serious secondary NTH). Non-traumatic headache (NTH) will be assessed and defined according to the ICHD-II-Criteria. Serious secondary NTH will be defined as a composite endpoint including different secondary NTH causes and entities as listed in the ICHD-II-Criteria.
3 secondary outcomes
clinical outcome of patients
Time frame: study entry and 3-month-interview
Additive benefit on sensitivity if copeptin and a diagnostic algorithm are combined
Time frame: study entry and 3-month-interview
Comparison of copeptin with other potential biomarkers in non-traumatic headache
Time frame: study entry and 3-month-interview
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 26 May 2014.
- Background: PubMed 20035506Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, Bingisser R, Muller K, Meckel S, Gass A, Kappos L, Steck AJ, Engelter ST, Muller B, Christ-Crain M. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann Neurol. 2009 Dec;66(6):799-808. doi: 10.1002/ana.21783.
- Background: PubMed 18355399Katan M, Muller B, Christ-Crain M. Copeptin: a new and promising diagnostic and prognostic marker. Crit Care. 2008;12(2):117. doi: 10.1186/cc6799. Epub 2008 Mar 6.
- Background: PubMed 19555842Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, Bergmann A, Potocki M, Noveanu M, Breidthardt T, Christ A, Boldanova T, Merki R, Schaub N, Bingisser R, Christ M, Mueller C. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009 Jun 30;54(1):60-8. doi: 10.1016/j.jacc.2009.01.076.
- Background: PubMed 17210203Friedman BW, Hochberg ML, Esses D, Grosberg B, Corbo J, Toosi B, Meyer RH, Bijur PE, Lipton RB, Gallagher EJ. Applying the International Classification of Headache Disorders to the emergency department: an assessment of reproducibility and the frequency with which a unique diagnosis can be assigned to every acute headache presentation. Ann Emerg Med. 2007 Apr;49(4):409-19, 419.e1-9. doi: 10.1016/j.annemergmed.2006.11.004. Epub 2007 Jan 8.
- Background: PubMed 18545909Grimaldi D, Cevoli S, Cortelli P. Headache in the emergency department. How to handle the problem? Neurol Sci. 2008 May;29 Suppl 1:S103-6. doi: 10.1007/s10072-008-0899-0.
- Derived from this study: PubMed 28197843Blum CA, Winzeler B, Nigro N, Schuetz P, Biethahn S, Kahles T, Mueller C, Timper K, Haaf K, Tepperberg J, Amort M, Huber A, Bingisser R, Sandor PS, Nedeltchev K, Muller B, Katan M, Christ-Crain M. Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study. J Headache Pain. 2017 Dec;18(1):21. doi: 10.1186/s10194-017-0733-2. Epub 2017 Feb 13.
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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.
Mirjam Christ-Crain, MD, PhD principal investigator
Department of Endocrinology, University Hospital of Basel, Switzerland
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 Head Pain, run by University Hospital, Basel, Switzerland at 2 sites in Switzerland.
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 2 inclusion and 2 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 26 May 2014. 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 Switzerland. 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?
Differentiation between serious secondary non-traumatic headache as opposed to benign, self-limiting non-traumatic headache by copeptin level measurement (time frame: At study entry, assessment of baseline characteristics, questionnaire, further investigations done by attending physician, and blood collection for copeptin measurement. telephone interview after 3 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01174901, which also lists 6 linked publications.
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 26 May 2014.