The Oxford Marfan Trial

NCT01949233 | Unknown Phase 2

• 1 other identifier: 2010-023612-14
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of the trial is to estimate the effects of allocation to irbesartan, or doxycycline, or a combination of both irbesartan and doxycycline, compared with placebo, on measures of elastic function of the aorta in people with the Marfan syndrome and enlargement of the aorta.

Conditions

Marfan Syndrome

Outcome Measures

Primary Outcomes (1)

• Change (i.e. difference between first and last study visits) in aortic distensibility in the ascending aorta between allocation arms measured using CMR

  0 months and 6 months

Secondary Outcomes (11)

• 1. Change in aortic distensibility in the proximal and distal descending aorta between allocation arms measured using CMR

  0 and 6 months

• 2. Change in aortic dimensions in the proximal and distal descending aorta

  0 and 6 months

• 3. Change in mean and peak axial and mean and peak circumferential aortic wall shear stress between allocation arms estimated by CMR using a 4D flow sequence

  0 and 6 months

• 4. Change in peripheral (brachial) blood pressure between allocation arms measured using a calibrated, validated automated sphygmomanometer

  0 and 6 months

• 5. Change in central blood pressure, and augmentation index between allocation arms measured by applanation tonometry and by oscillometric sphygmomanometry

  0 and 6 months

Study Arms (4)

Irbesartan 150-300mg (and doxycycline placebo)

EXPERIMENTAL

Irbesartan 150-300mg capsules daily for 6 months Doxycycline placebo capsules daily for 6 months

Drug: Irbesartan 150-300mg capsules daily for 6 months; Drug: Doxycycline placebo capsules daily for 6 months

Doxycycline 100-200mg (and irbesartan placebo)

EXPERIMENTAL

Doxycycline 100-200mg capsules daily for 6 months Irbesartan placebo capsules daily for 6 months

Drug: Doxycycline 100-200mg capsules daily for 6 months; Drug: Irbesartan placebo capsules daily for 6 months

Irbesartan 150-300mg and doxycycline 100-200mg

EXPERIMENTAL

Irbesartan 150-300mg capsules daily for 6 months Doxycycline 100-200mg capsules daily for 6 months

Drug: Irbesartan 150-300mg capsules daily for 6 months; Drug: Doxycycline 100-200mg capsules daily for 6 months

irbesartan and doxycycline placebo

PLACEBO COMPARATOR

Irbesartan placebo capsules daily for 6 months Doxycycline placebo capsules daily for 6 months

Drug: Doxycycline placebo capsules daily for 6 months; Drug: Irbesartan placebo capsules daily for 6 months

Interventions

Irbesartan 150-300mg capsules daily for 6 months DRUG

Irbesartan 150-300mg (and doxycycline placebo); Irbesartan 150-300mg and doxycycline 100-200mg

Doxycycline 100-200mg capsules daily for 6 months DRUG

Doxycycline 100-200mg (and irbesartan placebo); Irbesartan 150-300mg and doxycycline 100-200mg

Doxycycline placebo capsules daily for 6 months DRUG

Irbesartan 150-300mg (and doxycycline placebo); irbesartan and doxycycline placebo

Irbesartan placebo capsules daily for 6 months DRUG

Doxycycline 100-200mg (and irbesartan placebo); irbesartan and doxycycline placebo

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For those aged greater than or equal to 16 years of age at the time of enrolment, participant is willing and, in the opinion of the investigator, able to give informed consent for participation in the trial
• For those aged 13-15 at the time of enrolment, participant is willing and, in the opinion of the investigator, able to give informed assent, and parent/guardian is willing and able to give informed consent for participation in the trial.
• Weight ≥ 50kg
• Diagnosed with Marfan syndrome according to the revised Ghent criteria 1996
• Dilated aorta (BSA-adjusted aortic root z-score ≥2 at the aortic sinuses of Valsalva, using the method of Roman et al, or an absolute aortic root dimension \>4.0cm at the sinuses of Valsalva measured using either echocardiography or CMR)
• If the participant is a female of child-bearing potential, they are willing to ensure effective contraception as defined in the contraception policy
• If the participant is taking β-blocker therapy, they are willing to stop taking these one week prior to each CMR scan
• Willing and, in the investigator's opinion, able to comply with all trial requirements
• Willing to allow his or her General Practitioner and if appropriate, Consultant, to be informed of his or her participation in the trial and of any clinical findings or issues which may arise

You may not qualify if:

• Female who is pregnant
• Female who is planning pregnancy within 6 months of enrolment
• Female who is breast feeding
• Previous aortic dissection
• Previous aortic surgery
• Bicuspid or unicuspid aortic valve
• Scheduled elective cardiac or aortic surgery within 6 months of enrolment
• Definite diagnosis of Loeys-Dietz or Shpritzen-Goldberg syndrome
• Known bilateral renal artery stenosis or renal artery stenosis to a single functioning kidney
• History of idiopathic intracranial hypertension
• Exposure to angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, or medications containing these compounds in the 3 months prior to enrolment in the trial
• Absolute indication for angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, doxycycline or other antibiotics of the tetracycline class at enrolment
• Taking β-blocker therapy for an indication other than the Marfan syndrome
• Participant has participated in another research study involving an investigational medicinal product or device in the 3 months prior to enrolment
• Renal impairment of a moderate or severe degree (eGFR \<60 mls/min/1.73m2)

Sponsors & Collaborators

• University of Oxford: lead
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (2)

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

University of Oxford

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

MeSH Terms

Conditions

Marfan Syndrome

Interventions

Irbesartan; Doxycycline

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons

Study Officials

• J Colin Forfar, BSc (hons), MA(Oxon), MD, PhD,

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hayley Harvey

CONTACT

hayley.harvey@cardiov.ox.ac.uk

Alex Pitcher, MA (Oxon),DPhil, BM Mch, MRCP

CONTACT

alex.pitcher@cardiov.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2013
• First Posted: September 24, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2017
• Last Updated: June 9, 2015

Record last verified: 2015-06

Locations

GB (2)