Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
1,600
Countries
1
Sites
6
Ectopic pregnancy
To evaluate if the combination of mifepristone and letrozole is non-inferior to methotrexate in treating ectopic pregnancy within a non-inferiority margin of 10%.
Key facts
- Sponsor
- Karolinska Institutet
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Female
- Therapeutic area
- Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
- Trial duration
- 15 Dec 2023 → ongoing
- Decision date (initial)
- 2023-07-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Veteskapsrådet MILE-projektet
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
To evaluate if the combination of mifepristone and letrozole is non-inferior to methotrexate in treating ectopic pregnancy within a non-inferiority margin of 10%.
Secondary objectives 6
- To evaluate if there is any difference in treatment related side effects when using the combination of mifepristone and letrozole compared to methotrexate.
- To evaluate if there are differences in the proportion of patients who need additional medical and/or surgical interventions between the groups.
- To evaluate if there is difference in time to treatment response between the groups.
- To evaluate if there is difference in post treatment pregnancy rate and ovarian reserve between the groups.
- To evaluate if there are biomarkers for ectopic versus intrauterine pregnancy that can be identified.
- To evaluate if there are background factors that are associated with successful treatment.
Conditions and MedDRA coding
Ectopic pregnancy
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Confirmed ectopic pregnancy, or high suspicion thereof*, in need of treatment. *i.e. empty uterus, pathological hCG dynamic.
- 18 years old or above
- Able to understand verbal and written patient information
- Given written consent to participate in the trial
Exclusion criteria 6
- hCG-levels >5000 IU/L
- Heterogenous adnexal mass >35mm
- Fetal heart pulsation
- Signs of rupture such as large amount of free fluid in the abdomen, severe abdominal pain or hemodynamically unstable
- Heterotopic or atypical (cesarean scar pregnancy, cornual, intramural, cervical or abdominal pregnancy) extrauterine pregnancy
- Contraindications* to methotrexate, letrozole or mifepristone. * Allergy, severe liver disease (ALT/AST doubled, kidney disease (GFR <60ml/min), bone marrow suppression, active ulcer, severe stomatitis, breastfeeding, severe infection, chronic adrenal insufficiency, porphyria, uncontrolled asthma, active cancer treatment, ongoing treatment for psychosis, anticoagulants, high alcohol consumption
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the proportion of patients who have a successful treatment response defined as decline of serum hCG to < 2 IU/L without the need for any additional medical or surgical intervention within 60 days of treatment.
Secondary endpoints 6
- The proportion of patients in both groups with adverse events (AE) and serious adverse events (SAE) classified as related or possibly related to treatment as judged by the investigators.
- The proportion of patients who need additional medical or surgical interventions in each group.
- Time to resolution (days) of ectopic pregnancy from start of medical treatment to resolution defined as hCG <2 IU/L.
- AMH-levels at baseline, 1 month and 3 months after treatment. We will also assess time to pregnancy (days) and pregnancy rates (%) within the first year after treatment.
- Micro RNAs (analyzed by single cell sequencing) profiles and CA-125 (patients receiving treatment for ectopic pregnancy versus patients with ultrasound confirmed intrauterine pregnancy within the same period of gestation).
- Comparison of background factors between patients that have successful and unsuccessful treatment.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Letrozole Sandoz 2,5 mg filmdragerade tabletter
PRD747119 · Product
- Active substance
- Letrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 10 Day(s)
- Authorisation status
- Authorised
- ATC code
- L02BG04 — LETROZOLE
- Marketing authorisation
- 43311
- MA holder
- SANDOZ A/S
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD8503344 · Product
- Active substance
- Mifepristone
- Substance synonyms
- RU-486
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- G03XB01 — MIFEPRISTONE
- Marketing authorisation
- 11642
- MA holder
- EXELGYN SA
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
Methotrexate Teva 100 mg/ml koncentrat till infusionsvätska, lösning
PRD667056 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BA01 — METHOTREXATE
- Marketing authorisation
- 10155
- MA holder
- TEVA SWEDEN AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Karolinska Institutet
- Sponsor organisation
- Karolinska Institutet
- Address
- Nobels Vag 6
- City
- Solna
- Postcode
- 171 65
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska Institutet
- Contact name
- Kristina Gemzell Danielsson
Public contact point
- Organisation
- Karolinska Institutet
- Contact name
- Kristina Cederblad
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Karolinska University Hospital ORG-100000573
|
Stockholm, Sweden | Code 10 |
| Karolinska University Hospital ORG-100000573
|
Stockholm, Sweden | On site monitoring |
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Sweden | Ongoing, recruiting | 1,400 | 6 |
| Rest of world
Thailand, Nepal
|
— | 200 | — |
Investigational sites
Uppsala University Hospital
Department of Women's and children's health, Akademiska Sjukhuset, 751 85, Uppsala
Region Oerebro Laen
Institutionen för medicinsk vetenskap, kvinnokliniken, Sodra Grev Rosengatan, 701 85, Orebro
Soedersjukhuset AB
VO Kvinnosjukvård och förlossning, Sjukhusbacken 10, Hogalid, Stockholm
Karolinska University Hospital
Obstetrics and Gynecology, Halsovagen, Flemingsberg, Huddinge
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Obstetrics and Gynecology, Bla Straket 5, 413 46, Goteborg
Region Vaesterbotten
Obstetrics and Gynecology, Koksvagen 11, Alidhem, Umea
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Sweden | 2023-12-15 | 2024-03-08 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 14 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | CLINICAL TRIAL PROTOCOL v2 230630_Public Use_Clean | 2 |
| Protocol (for publication) | D5_CLINICAL TRIAL PROTOCOL 2023-503935-16-00 v2_2026-03-04_Clean-Public | 2 |
| Protocol (for publication) | MILE Clinical Trial Protocol Version 1 Including Appendix 1_Public Use | 1 |
| Recruitment arrangements (for publication) | MILE forfarande-for-rekrytering-och-samtyckesprocess | 2 |
| Subject information and informed consent form (for publication) | Kort utvardering av patientnojdhet SAPS_Svenska | 1 |
| Subject information and informed consent form (for publication) | MILE Forskningspersonsinformation Version 1 | 2 |
| Subject information and informed consent form (for publication) | MILE-Daglig dagbok Version 1 | 1 |
| Subject information and informed consent form (for publication) | SMILE Forskningspersonsinformation kontrollgrupp Version 1_Public Use | 2 |
| Subject information and informed consent form (for publication) | SMILE Forskningspersonsinformation substudie RCT Version 1_Public Use | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC Letrozole Sandoz film-coated tablet Swedish | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC Methotrexate Teva concentrate for solution for infusion Swedish | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC Mifegyne tablet Swedish | 1 |
| Synopsis of the protocol (for publication) | MILE Protkoll Synopsis_Svenska | 1 |
| Synopsis of the protocol (for publication) | MILE Protokoll Synopsis v2 Svenska clean | 2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-05-04 | Sweden | Acceptable 2023-07-19
|
2023-07-21 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2026-01-16 | Sweden | Acceptable 2026-03-25
|
2026-03-25 |