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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud University Medical Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

19 Mar 2024 → ongoing

Decision date (initial)

2023-09-14

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Health and Digital Executive Agency

External identifiers

EU CT number

2023-505239-10-00

WHO UTN

U1111-1291-5183

ClinicalTrials.gov

NCT05917275

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To identify MOMICs biomarkers that predict the response in 24-hour blood pressure to anti-hypertensive treatment for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine).

Secondary objectives 2

1. To identify MOMICs biomarkers that predict the response in night-time blood pressure to anti-hypertensive treatment for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine).
2. To identify MOMICs biomarkers that predict side effects including changes in QoL induced by olmesartan, amlodipine and hydrochlorothiazide

Conditions and MedDRA coding

Primary (essential) hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age 18 up to and including 75 years at the time of inclusion
2. 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)
3. Indication for antihypertensive therapy according to the 2023 European Society of Hypertension Guidelines for the management of arterial hypertension
4. 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.)
5. Subject is not treated with antihypertensive drugs or is treated with a single antihypertensive drug

Exclusion criteria 29

1. 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
2. History of severe valvular or structural heart disease (excluding left ventricular hypertrophy)
3. History of NYHA class III or IV heart failure or known reduced left ventricular function (ejection fraction (EF) <30%)
4. History of cerebrovascular accident or transient ischemic attack
5. History of hypertensive crisis
6. History of liver failure
7. History of skin cancer
8. History of gout
9. Current hyperparathyroidism
10. Current biliary tract obstruction
11. Pregnancy
12. 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)
13. Life expectancy < 1 year
14. Known side effect or contra-indication to treatment with calcium channel blcokers
15. Known side effect or contra-indication to treatment with angiotensin II receptor blockers
16. Known side effect or contra-indication to treatment with thiazide diuretics
17. Arm circumference > 46 cm
18. Sodium level outside reference range at screening visit
19. Potassium level outside reference range at screening visit
20. Calcium level outside reference range at screening visit
21. eGFR < 50 ml/min/1,73m2
22. Use of VEGF inhibitors, calcineurin inhibitors, glucocorticosteroids, erythropoietin stimulation agents, daily use of NSAID’s
23. Use of MDMA, methamphetamine, cocaine
24. 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)
25. Use of potassium containing supplements
26. 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).
27. History of myocardial infarction, angina pectoris
28. History of atrial fibrillation
29. Use of loop diuretics

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Predictive value of a MOMICs profile to discriminate subjects with a decrease in 24-hour blood pressure below the median from subjects with a decrease in 24-hour blood pressure above the median for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine).

Secondary endpoints 2

1. Predictive value of a MOMICs profile to discriminate subjects with a decrease in night-time blood pressure below the median from subjects with a decrease in 24-hour blood pressure above the median, for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine).
2. Correlation between changes in individual biomarkers and adverse effects as documented using adverse effects questionnaire and SF-36

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud University Medical Center

Sponsor organisation

Stichting Radboud University Medical Center

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Internal Medicine Secretary

Public contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Internal Medicine Secretary

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications