Evaluation of the Efficacy of Valsartan in Slowing Down Aortic Root Dilatation in Children and Young Adults with Marfan

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

9 Feb 2024 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Research Agency (Agencja Badań Medycznych)

External identifiers

EU CT number

2024-515059-39-00

EudraCT number

2022-000513-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Evaluation of the efficacy of valsartan in slowing down aortic root dilatation in children and young adults with Marfan-type heritable thoracic aortic diseases

Secondary objectives 1

1. To evalute: - annual difference in the aortic root diameter expressed in z-scores, indexed to sex and body surface area (BSA), measured by transthoracic echocardiography and expressed as z-score/year, - the absolute annual difference in aortic root diameter expressed in millimetres as assessed by angio- CT, - absolute annual difference in the diameter of the aortic annulus, sinotubular junction, distal ascending aorta, aortic arch, thoracic aorta, and abdominal aorta assessed by transesophageal echocardiography and expressed in mm/year, - annual difference in the diameter of the aortic annulus, sinotubular junction, distal ascending aorta, aortic arch, thoracic aorta and abdominal aorta expressed in z-score (sex-indexed and BSA), assessed by transesophageal echocardiography and expressed as z-score/year, - difference in aortic root diameter in subgroups of patients with different types of HTAD, identified by genetic testing, - acute aortic syndromes: aortic dissection, aortic perforation, intramural hematoma, penetrating ulcer), aortic dilatation requiring surgery, death from cardiovascular causes, - adverse events related to / potentially related to the administered pharmacotherapy (serious adverse events - SAE, adverse events – AE), - comparison of systolic and diastolic blood pressure values based on Holter blood pressure measurements.

Conditions and MedDRA coding

Marfan Syndrome Diseases related to Marfan syndrome (rare diseases with aneurysms of the thoracic aorta and dissection of the aorta), among others: Loeys-Dietz syndrome, Vascular type of Ehlers-Danlos syndrome, Arterial Tortuosity syndrome, Shprintzen-Goldberg syndrome, Neonatal form of Marfan syndrome, Aneurysms-osteoarthritis syndrome, Multi-system smooth muscle dysfunction syndrome, Familial thoracic aortic aneurysms and aortic dissections, etc.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Age 1- 39 years. 2. Diagnosis of a syndrome classified under the HTAD group: • Marfan Syndrome • Diseases related to Marfan syndrome (rare diseases with aneurysms of the thoracic aorta and dissection of the aorta), among others: Loeys-Dietz syndrome, Vascular type of Ehlers-Danlos syndrome, Arterial Tortuosity syndrome, Shprintzen-Goldberg syndrome, Neonatal form of Marfan syndrome, Aneurysms-osteoarthritis syndrome, Multi-system smooth muscle dysfunction syndrome, Familial thoracic aortic aneurysms and aortic dissections, Bicuspid aortic valve syndrome - familial BAV. 3. Aortic root dilatation (z-score ≥ 2). 4. Signed informed consent to participate in the study.

Exclusion criteria 1

1. 1. Past aortic cardiac surgery. 2. Eligibility for aortic cardiac surgery at the time of examination. 3. Hemodynamically significant, severe or moderate aortic valve defect assessed by echocardiography. 4. Inability to obtain diagnostic echocardiographic images necessary for the evaluation of the aorta in a transthoracic echocardiographic examination - absence of the "Acoustic window". 5. Heart failure; defined as left ventricular ejection fraction <40%. 6. ARB therapy, unless 3 months have elapsed from the last dose taken before qualification. 7. Taking ACE inhibitors, unless 3 months have elapsed from the last dose taken before qualification. 8. Previous adverse reactions to valsartan or other ARB drugs. 9. Contraindications to valsartan (including hypersensitivity to the active substance or to any of the excipients, severe liver dysfunction, biliary cirrhosis, cholestasis, bilateral renal artery stenosis). 10. Breastfeeding, pregnancy or planning pregnancy in the next 12 months and for women of childbearing age, not on an effective method of contraception. 11. Known renal impairment as manifested by estimated creatinine clearance <30 ml/min in children and <10 ml/min in adults

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute annual difference in aortic t diameter measured by transthoracic echocardiography and expressed in mm/yearroo

Secondary endpoints 1

1. - annual difference in the aortic root diameter expressed in z-scores, indexed to sex and body surface area (BSA), measured by transthoracic echocardiography and expressed as z-score/year, - the absolute annual difference in aortic root diameter expressed in millimetres as assessed by angio- CT

Investigational products

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

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Chief Medical Officer; Principal Investigator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Director of Clinical Research Support Centre

Locations

1 EU/EEA country · 4 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 10 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