Predicting the effect of blood pressure lowering medication using Multi-Omics, a biomarker profile based on blood and urine analyses

Prior treatment

• Treatment with 2 or more antihypertensive drugs < 3 months before inclusion. It is not allowed to stop medication for study purposes in subjects treated with 2 or more anti-hypertensive drugs
• Known side effect or contra-indication to treatment with angiotensin II receptor blockers
• Known side effect or contra-indication to treatment with thiazide diuretics
• Use of VEGF inhibitors, calcineurin inhibitors, glucocorticosteroids, erythropoietin stimulation agents, daily use of NSAID’s
• Use of glycyrrhetinic acid containing products , i.e. liquorice, specific herbal teas, <4 weeks before inclusion. (If patients are willing to stop the intake of glycyrrhetinic acid containing products for the duration of the trial, they can be rescreened after 4 weeks of stopping glycyrrhetinic acid containing products)
• Concurrent use of medication or a supplement with significant drug interaction with study medication. Special attention is warranted for amlodipine which is metabolized by Cyp3A4. Subjects using strong inhibitors or inducers of Cyp3A4 are excluded from participation in this trial. A list of strong inhibitors and inducers is provided in Addendum 1 of the protocol. For information on possible drug interactions we refer to the website of Lexi-Interact Online (Lexicomp® Drug Interactions - UpToDate (doctorabad.com): https://doctorabad.com/UpToDate/d/di.htm).

Other illness

• Known diagnosis of secondary hypertension to an identifiable cause other than treated sleep apnea (e.g., hyperaldosteronism, renal artery stenosis, pheochromocytoma, Cushing's syndrome, coarctation of the aorta, uncontrolled hyper- or hypothyroidism and intracranial tumor)
• History of severe valvular or structural heart disease (excluding left ventricular hypertrophy)
• History of myocardial infarction, angina pectoris
• History of atrial fibrillation
• History of cerebrovascular accident or transient ischemic attack
• History of hypertensive crisis
• History of liver failure
• History of skin cancer
• History of gout

Lab values

• Known side effect or contra-indication to treatment with calcium channel blcokers
• Sodium level outside reference range at screening visit
• Potassium level outside reference range at screening visit
• Calcium level outside reference range at screening visit
• eGFR < 50 ml/min/1,73m2
• Use of potassium containing supplements
• History of NYHA class III or IV heart failure or known reduced left ventricular function (ejection fraction (EF) <30%)

Other

• Current biliary tract obstruction
• Pregnancy
• Life expectancy < 1 year
• Arm circumference > 46 cm
• Use of MDMA, methamphetamine, cocaine
• Use of loop diuretics
• Current hyperparathyroidism

• Age 18 up to and including 75 years at the time of inclusion
• 24 hours systolic blood pressure 130-164 (corresponding with grade 1-2 hypertension), without the use of blood pressure lowering agents (at screening for patients without pre-treatment or after 4 week wash-out of antihypertensive medication for subjects using a single antihypertensive agent at screening)
• Indication for antihypertensive therapy according to the 2023 European Society of Hypertension Guidelines for the management of arterial hypertension
• Female patients must be non-lactating and at no risk of pregnancy for one of the following reasons: 1 year postmenopausal, surgically sterile, or willing to use an acceptable method of contraception throughout the trial (oral contraceptives, approved contraceptive implants, long-term injectable contraception, intrauterine devices, or tubal ligation are allowed.)
• Subject is not treated with antihypertensive drugs or is treated with a single antihypertensive drug