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.

Inclusion Criteria:

• Male or female, aged 13 years or above at last birthday (note that there is no upper age limit for inclusion in this trial)
• 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

Exclusion Criteria:

• 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)
• Hyperkalaemia (>5.1 mmol/L)
• Significant hepatic impairment (ALT or AST >3 times upper limit of normal)
• History of allergic reaction or any other clinically significant intolerance to irbesartan or its constituents; other angiotensin receptor blockers / antagonists; angiotensin converting enzyme inhibitors, doxycycline or its constituents, or placebo medications or its constituents
• Contra-indications to MRI (e.g. implantable cardiac electronic device, claustrophobia, intracranial aneurysm clips and metallic ocular foreign bodies etc.)
• Participant currently required to take or likely to be required to start, in the 6 months following enrolment, a medicinal product which is known or suspected to interact, to a clinically significant extent, with irbesartan including: potassium supplementation, potassium sparing diuretics, lithium, regular use of antacids containing aluminium magnesium hydroxide
• Participant currently required to take or likely to be required to start, in the 6 months following enrolment, a medicinal product which is known or suspected to interact, to a clinically significant extent, with doxycycline including ergotamine and methysergide. This includes drugs known to induce the cytochrome P450 system to a clinically significant extent, including but not limited to, carbamazepine, phenytoin, rifampicin, griseofulvin, barbiturates or sulphonylureas.
• Alcohol dependence
• Any other significant disease, disorder or circumstance (e.g. terminal illness), which, in the opinion of the Investigator, may either put the participant at risk in the trial, or may introduce significant bias to the trial, or may affect the participant's ability to participate in the trial