A pilot study of enalapril in venous malformations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

30 Jan 2025 → ongoing

Decision date (initial)

2024-06-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Oslo university hospital

External identifiers

EU CT number

2023-510076-31-00

WHO UTN

U1111-1301-7400

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To explore the change of VM related pain.

Secondary objectives 3

1. To explore volume change of the VM
2. To explore change in quality of life in patients with VM
3. To investigate safety in patients with VM

Conditions and MedDRA coding

Venous malformation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with venous malformations verified by clinical examination, ultrasound and anatomic MRI with contrast. The venous malformation should have well defined borders and the volume should be measurable on MRI. Diagnosis of venous malformation shall be object for consensus in a multidisciplinary team meeting.
2. Patients must experience pain from the malformation. Pain is defined as local pain in the malformation, and the participant must have pain that according to the patient inhibits daily activity or pain during nighttime that interferes with sleep. The symptoms has to reduces quality of life. NRS inclusion criteria is greater or equal to 4
3. Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
4. Negative urine pregnancy test in females with childbearing potential. A woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
5. Woman of childbearing potential (WOCBP) must use highly effective contraception measures while on study medicine and for up to 2 weeks past treatment. Highly effective birth control methods include:  Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation.  Progestogen-only hormonal contraception associated with inhibition of ovulation  Intrauterine device (IUS)  Intrauterine hormone-releasing system (IUS)  Bilateral tubal occlusion  Vasectomized partner  Sexual abstinence (controlled with regular questioning by PI)
6. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF). They must also be capable of answer adequately questionnaires regarding quality of life. Since the questionnaire are validated in Norwegian and English, they also should control one of this language.

Exclusion criteria 17

1. Diffuse VM with no defined borders.
2. Use of mTOR-inhibitor, racekadotril, sacubitril/valsartan, ramipril or vildagliptin is contraindicated because of an elevated risk of angioedema
3. Use of angiotensin-II receptor antagonist or alsikiren (direct renin inhibitor) is contraindicated because of increased risk of hypotension, hyperkalemia, and impaired renal function.
4. Impaired cardiac function and clinically significant cardiac disease including aorta- and mitral valve stenosis and hypertrophic cardiomyopathy.
5. Lactose intolerance, total lactase deficiency or glucose-galactose malabsorption because Enalapril contains lactose.
6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the ACE-inhibitor (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea > grade 2, malabsorption syndrome, or small bowel resection.)
7. Hypersensitivity to the active substance or any of the excipients listed in section 6.1 of the SmPC of the SmPC of enalpril or to other ACE-inhibitors.
8. Patients with a history of angioneurotic edema related to previous treatment with ACE-inhibitors and patients with Hereditary or ideopatic anigioneurotic edema
9. Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, contraindicated participation in the clinical study
10. Known renal artery stenosis
11. BMI > 30
12. Impaired renal function (eGFR < 50 ml/min/1,73m2)
13. Pregnant or lactating woman
14. Any condition that in the view of the investigator would suggest that the patient is unable to comply with the study protocol and procedures.
15. Known diabetes because of the risk of hypoglycemia.
16. Impaired liver function (INR > 1,5 or aminotransferases > 3 times upper limit of normal)
17. 13. Contraindications for MRI (cardiac pacemaker or defibrillator, intracranial clips, cochlear implants or other metallic foreign bodies, claustrophobia.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in NRS score 12 months after treatment start with enalapril compared to baseline.

Secondary endpoints 3

1. Volume change on MRI 12 months after treatment start with enalapril compared to baseline.
2. Change in Quality of life 12 months after treatment start with enalapril compared to baseline.
3. Register adverse events > or equal to grade 2 and side effects continues during the study

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Christina Bjerring Opheim

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Christina Bjerring Opheim

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 8 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