Optimal medical treatment of difficult-to-treat hypertension.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 Oct 2023 → ongoing

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-517628-20-00

EudraCT number

2021-006327-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Phase A:
- Percentage of patients with uncontrolled BP confirmed on ABPM (24h mean, SBP ≥125 mm Hg or DBP ≥80 mm Hg)
Phase B:
- Percentage of patients with controlled BP after 12 weeks of treatment with triple SPC, confirmed on ABPM (24h mean, SBP <125 mm Hg and DBP <80 mm Hg) – as the efficacy of the treatment strategy (switching ineffective treatment to triple SPC) – the whole group and P+I+A and E+H+A groups separetly.
Phase C:
- Magnitude of reduction of SBP on ABPM (24h mean) after 12 weeks of treatment – comparison of eplerenone vs spironolactone and torasemide vs spironolactone.

Secondary objectives 1

1. Phase A: - Percentage of patients with BP controlled confirmed by HBPM (mean over the period of 6 days, SBP ≥130 mm Hg or DBP ≥80 mm Hg) - Consistency of the rate of uncontrolled BP between ABPM and HBPM Phase B: - Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by OBPM (SBP <130 mm Hg and DBP <80 mm Hg). - Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by HBPM (mean over 6 days, SBP <130 mm Hg and DBP <80 mm Hg). Phase C: - Changes of SBP on ABPM (24h mean) after 12 weeks of treatment in patients receiving spironolactone, eplerenone or torasemide as compared against baseline.

Conditions and MedDRA coding

hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Women and men
2. Age: ≥18 years old, less than 75 years old
3. Documented history of HT
4. HT treated for at least six months
5. Office BP ≥ 130 and / or ≥80 mm Hg (average seated BP at Visit 1)
6. Use of 3 or more antihypertensive drugs, including an angiotensin converting enzyme inhibitor / angiotensin II receptor blocker (ACEi/ARB) and a thiazide/thiazide-like diuretic (TD/TLD) or loop diuretic (single drugs or double SPCs) (any association) or a threecomponent SPC based on drugs other than those used in the study)
7. Stable antihypertensive treatment regimen – no changes in antihypertensive treatment strategy at least for 4 weeks
8. Able and willing to comply with all study procedures and able to attend one of the study centers

Exclusion criteria 25

1. Inability to give informed consent
2. Office SBP ≥180 mm Hg and/or DBP ≥110 mm Hg and/or DBP <60 mm Hg
3. BMI ≥45 kg/m2
4. eGFR of <45 mL/min/1.73 m2
5. Potassium serum concentration > 5 mmol/L or < 3.5 mmol/L within the year prior to the screening visit
6. Persistent hyponatremia or history of hyponatremia related to TD/TLD treatment (sodium concentration <135 mmol/L)
7. Secondary or accelerated hypertension (not including sleep apnea)
8. Chronic glucocorticoid therapy
9. Myocardial infarction or cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) in the year prior to study inclusion
10. Heart failure with an ejection fraction ≤50%
11. Cardiomyopathy
12. Severe valvular disease
13. Aortic aneurysm
14. Prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta blockers) for other chronic conditions (e.g. chronic coronary syndromes) such that discontinuation might pose serious risk to health
15. Documented history of persistent or permanent atrial tachyarrhythmia requiring beta-blocker treatment
16. Primary pulmonary hypertension
17. Decompensated hyperthyroidism or hypothyroidism
18. Severe liver dysfunction (alanine aminotransferase and/or asparagine aminotransferase activity ≥3 times the upper limit of normal value)
19. Documented contraindication or allergy to studied drugs
20. Limited life expectancy of < 1 year at the discretion of the Investigator
21. Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements
22. All women of child bearing potential; women of child bearing potential can be included in the study ONLY after providing documentation of effective contraception (intrauterine device, hormone therapy);
23. Concurrent enrollment in any other investigational drug or device trial
24. Anticipated change of medical status during the trial (e.g., surgical intervention requiring >2 weeks convalescence)
25. Current therapy for cancer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. • Phase A The variable quantifying the efficacy of current antihypertensive treatment will be the percentage of patients with uncontrolled BP (24h mean SBP values ≥ 125 mm Hg or 24h mean DBP values ≥ 80 mm Hg) in relation to the ITT-A size.
2. • Phase B The efficacy of switching of the previous drug regimen to a triple SPC (as the efficacy of the treatment strategy) and of each of two triple SPC drugs (P+I+A group and O+H+A, as the efficacy of each triple SPC) will be measured as the percentages of patients who achieve BP control defined as 24h mean SBP values < 125 mm Hg and 24h mean DBP values < 80 mm Hg). These would be assessed at the Visit 5 after 12 weeks of treatment in the ITT-B data set.
3. • Phase C The main analysis of the differences in the change from baseline (Visit 6) to week 12 (Visit 8) in mean 24h SBP measured on ABPM between the groups will be conducted on the PP set. ABPM measurements obtained after premature discontinuation of treatment will be excluded from this analysis (i.e., considered as missing, not included to PP set). The treatment groups of patients in this analysis are eplerenone group, torasemide group and spironolactone group.

Secondary endpoints 2

1. Phase A: - Percentage of patients with BP controlled confirmed by HBPM (mean over the period of 6 days, SBP ≥130 mm Hg or DBP ≥80 mm Hg)
2. Phase A: - Consistency of the rate of uncontrolled BP between ABPM and HBPM

Investigational products

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

Test 7

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Sponsor organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Address

Alpejska 42

City

Warsaw

Postcode

04-628

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Contact name

Clinical Research Support Centre Information Desk

Public contact point

Organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Contact name

Clinical Research Support Centre Information Desk

Third parties 4

Locations

1 EU/EEA country · 20 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 31 files

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

Application history

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