Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001616864
Ethics application status
Approved
Date submitted
21/10/2021
Date registered
26/11/2021
Date last updated
29/08/2022
Date data sharing statement initially provided
26/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
An evaluation of the efficacy of eptinezumab in the inpatient management of status migrainosus in comparison to intravenous lignocaine in patients who have failed other therapies
Scientific title
An evaluation of the efficacy of eptinezumab in the inpatient management of status migrainosus in comparison to intravenous lignocaine in patients who have failed other therapies
Secondary ID [1] 305613 0
None
Universal Trial Number (UTN)
Trial acronym
SMITE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 324044 0
Condition category
Condition code
Neurological 321551 321551 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised, double-blinded parallel group controlled study to evaluate the safety and efficacy of eptinezumab against lignocaine in the inpatient treatment of status migrainosus.

Participants randomised to the Eptinezumab arm will receive 300mg via intravenous infusion over 30 minutes followed by placebo infusion (saline) for up to five days or until the migraine is aborted.
Intervention code [1] 322016 0
Treatment: Drugs
Comparator / control treatment
The control treatment for this study is lignocaine as per standard treatment for status migrainosus at the study site.

Participants randomised to the lignocaine arm will receive a placebo (saline) intravenous infusion for 30 minutes followed by lignocaine 2mg/min via intravenous infusion for up to five days (as per site standard procedure) or until the migraine has been aborted.

The placebo infusion for both groups will be identical.
Control group
Active

Outcomes
Primary outcome [1] 329318 0
Time from treatment initiation to discharge. Information collected by daily contact with participant during admission and confirmation from discharge confirmation in medical records.
Timepoint [1] 329318 0
At time of acute hospital discharge
Primary outcome [2] 329319 0
Visual Analogue Scale (VAS) of pain associated with migraine
Timepoint [2] 329319 0
Day 1, Day 2, Day 3, Day 4 and Day 5 of admission
Primary outcome [3] 329320 0
Use of rescue medications during admission collected via participant medical records
Timepoint [3] 329320 0
At time of acute hospital discharge
Secondary outcome [1] 402115 0
Healthcare Utilisation (primary health care provider visits and emergency department presentations) will be assessed as a composite secondary outcome. Information regarding healthcare utilisation will be collected from participants three months following their discharge from hospital.
Timepoint [1] 402115 0
90 days following discharge from hospital
Secondary outcome [2] 402116 0
Migraine Disability Assessment (MIDAS)
Timepoint [2] 402116 0
Day 1 of participation (prior to initiation of treatment) and day 90 following discharge from hospital
Secondary outcome [3] 402127 0
Safety of intervention based on laboratory (hematology and chemistry evaluation of blood samples) and vital signs assessments; blood pressure (digital blood pressure cuff), heart rate (pulse oximeter), temperature (thermometer), respiratory rate (visual assessment).
Timepoint [3] 402127 0
Day 1, day 2, day 3, day 4 and day 5 of participation in the study and day 90 following participants' discharge from hospital
Secondary outcome [4] 402835 0
Headache Impact Test (HIT- 6)
Timepoint [4] 402835 0
Day 1 of participation (prior to initiation of treatment) and day 90 following discharge from hospital
Secondary outcome [5] 402836 0
Work Productivity and Activity Impairment Questionnaire (WPAI)
Timepoint [5] 402836 0
Day 1 of participation (prior to initiation of treatment) and day 90 following discharge from hospital
Secondary outcome [6] 402837 0
Health related quality of life (EA-5D)
Timepoint [6] 402837 0
Day 1 of participation (prior to initiation of treatment) and day 90 following discharge from hospital

Eligibility
Key inclusion criteria
- Aged 18 to 65 inclusive at time of presentation to ED
- At least a 1-year history of migraine with or without aura as per the ICHD-3 criteria
- Age of participant at the time of migraine onset <50 years old
- An acute migraine attack that has persisted for greater than or equal to 72 hours as per the ICHD-3 criteria for status migrainosus
- Ongoing symptoms despite, or contraindication to, triptan and chlorpromazine therapy
- In the opinion of the investigator and treating doctor, adequate investigation and consideration has been given for secondary causes of headache prior to enrolment.
- Written informed consent obtained from the participant prior to any study-related procedures
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of hemiplegic migraine, cluster headache or other trigeminal autonomic cephalalgia
- Current concomitant diagnosis of a secondary type of headache
- Chronic headache with continuous pain lasting more than three weeks
- Headache, which in the opinion of the investigator or delegate requires further investigation for secondary causes of headache
- Any clinically significant hematologic, endocrine, pulmonary, hepatic, gastrointestinal or neurologic disease
- Received an anti-CGRP product within 6 months
- History of known hepatic disease with potential for hepatic function impairment
- History of myocardial infarction, stroke, transient ischaemic attack, unstable angina or revascularisation procedure
- Cardiac arrythmia
- Newly diagnosed or uncontrolled hypertension
- Currently received treatment for another investigational drug or within 5 half-lives since ending treatment of another investigational drug.
- Clinically significant confounding pain disorder
- Uncontrolled or untreated major psychiatric condition
- BMI >39kg/m2
- Women who are pregnant, breastfeeding or planning to become pregnant during the study
- Previous ADR to lignocaine or other local anaesthetics
- History of malignancy (other than non-melanoma skin cancer, fully treated by excision)
- Previously received intravenous lignocaine for status migrainosus
- Need for contraindicated pro-arrhythmic or QT prolonging medication contraindicating lignocaine infusion

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/11/2021
Actual
27/04/2022
Date of last participant enrolment
Anticipated
15/11/2022
Actual
Date of last data collection
Anticipated
20/03/2023
Actual
Sample size
Target
40
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 20822 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 35647 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 309975 0
Hospital
Name [1] 309975 0
Alfred Hospital
Country [1] 309975 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road
Melbourne, VIC 3004
Country
Australia
Secondary sponsor category [1] 311023 0
None
Name [1] 311023 0
Address [1] 311023 0
Country [1] 311023 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309685 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 309685 0
Level 5, 553 St Kilda Rd
Melbourne VIC 3004
Ethics committee country [1] 309685 0
Australia
Date submitted for ethics approval [1] 309685 0
26/07/2021
Approval date [1] 309685 0
17/09/2021
Ethics approval number [1] 309685 0
77323 Local Project 443/21

Summary
Brief summary
This study is a randomised, double-blinded parallel group controlled study to evaluate the safety and efficacy of eptinezumab against lignocaine in the inpatient treatment of status migrainosus. Subjects who fulfil the International Classification of Headache Disorders, third edition criteria of migraine and status migrainosus and who have failed or are inappropriate to receive triptan and chlorpromazine therapy will be enrolled into this trial.

Upon randomisation, forty subjects will be allocated in a 1:1 ratio to receive either eptinezumab 300mg or placebo infusion, and admitted to hospital to receive intravenous lignocaine as standard medical therapy (if they received a placebo infusion on randomisation), or a placebo infusion for up to five days, or until their migraine is successfully treated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115038 0
Dr Jason Ray
Address 115038 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 115038 0
Australia
Phone 115038 0
+61 390762470
Fax 115038 0
Email 115038 0
[email protected]
Contact person for public queries
Name 115039 0
Ms Georgia Ramsay
Address 115039 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 115039 0
Australia
Phone 115039 0
+61 390762470
Fax 115039 0
Email 115039 0
[email protected]
Contact person for scientific queries
Name 115040 0
Dr Jason Ray
Address 115040 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 115040 0
Australia
Phone 115040 0
+61 390762470
Fax 115040 0
Email 115040 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual participant data, after de-identification.
When will data be available (start and end dates)?
Between 3 months and 5 years following publication of findings
Available to whom?
Researchers who request access backed by a methodologically sound proposal
Available for what types of analyses?
Those outlined in an approved proposal
How or where can data be obtained?
By arrangement with the corresponding author via [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseStatus migrainosus inpatient treatment with eptinezumab (SMITE): Study protocol for a randomised controlled trial.2022https://dx.doi.org/10.1136/bmjopen-2021-059647
N.B. These documents automatically identified may not have been verified by the study sponsor.