(WHAT!) – RCT: Open-label randomized controlled trial for the effects of continuous daily use of ethinylestradiol/levonorgestrel (30/150 µg/day) compared with vitamin E (400 IU/day) in the treatment of menstrually-related migraine and perimenopausal migraine

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hersenstichting · Leiden University Medical Center · ZonMW

External identifiers

EU CT number

2024-517127-40-00

EudraCT number

2018-004096-12

ClinicalTrials.gov

NCT04007874

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis, Efficacy

To evaluate the effect of continuous daily use of ethinylestradiol/levonorgestrel (30/150 pg/day) compared with vitamin E (400 lU/day) in women:
1. Trial 1: with menstrually-related migraine or pure menstrual migraine;
2. Trial 2: with perimenopausal migraine.
The primary efficacy endpoint for the trials is the mean change from baseline in mean monthiy migraine days in a 28-day period as assessed at the 12-week timepoint (weeks 9-12).

Secondary objectives 1

1. Secondary efficacy endpoints are defined as the mean change from baseline in a 28-day period as assessed at the 12-week timepoint (week 9-12): • Number of headache days • Number of migraine or probable migraine attacks • 50% responders, defined as patients who had >50% reduction in the number of migraine days. Secondary safety endpoints are; • Occurrence of adverse events and serious adverse events.

Conditions and MedDRA coding

Migraine

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Trial 1: Menstrually-related migraine: Female - Age ^ 18 - Menstrually-related migraine or pure menstrual migraine - Demonstrated at least 80% compliance with eDiary during baseline period - No or stable for at least two months on prophylactic medication Trial 2: Perimenopausal migraine: Female - AgeS 18 In the early menopausal transition phase (a difference of 7 days or more in length of consecutive cycles, which should occur at least twice in a period of 12 menstrual cycles) - Demonstrated at least 80% compliance with eDiary during baseline period - No or stable for at least two months on prophylactic medication

Exclusion criteria 1

1. - Smoking - Migraine with aura - Chronic migraine with 15 or more headache days per month/with 8 or more migraine days per month - Medication-overuse headache (ICHD-3 criteria) - Women who are breastfeeding, pregnant, or planning to become pregnant - Oral contraceptive use and not willing to undergo washout period (stop for two consecutive months) - Vitamin E use at start of the study - Use of other sex hormone containing treatments - Increased risk of VTE: history of VTE or thrombophlebitis, hereditary predisposition for VTE (APC resistance, protein C or S deficiency, antithrombin deficiency), VTE in first-degree family member at young age, long term immobilisation - Increased risk of ATE: history of ATE, hereditary predisposition for ATE (hyperhomocysteinemia, antiphospholipid antibodies), ATE in first-degree family member at young age, diabetes mellitus, total cholesterol ≥ 6.5 - Other contraindication for oral contraceptives: liver malignancy, schistosomiasis, HIV/aids, use of immunosuppressives, tuberculosis, sex-hormone-dependent malignancies (breast, endometrial or ovary carcinomas), pancreatitis, vaginal bleeding with unknown cause, other diseases that can influence vessels (malignancies, heart valve disorders, atrial fibrillation, SLE, haemolytic uremic syndrome, chronic inflammatory bowel disease, sickle cell disease) - Contraindication for vitamin E: vitamin K deficiency - Hypersensitivity for any of the compounds in oral contraceptive or vitamin E - Spontaneous postmenopausal status (menstrual bleedings have ceased for 12 consecutive months) - Iatrogenic postmenopausal status - Inability to complete the electronic diary in an accurate manner - Any serious illness that can compromise study participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. mean change from baseline in mean monthly migraine days in a 28-day period as assessed at the 12-week timepoint (weeks 9–12).

Secondary endpoints 1

1. mean change from baseline in a 28-day period as assessed at the 12-week timepoint (week 9-12): • Number of headache days • Number of migraine or probable migraine attacks • 50% responders, defined as patients who had ≥50% reduction in the number of migraine days.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Gisela Terwindt

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Gisela Terwindt

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications