Clinical trial NCT06275763: Optimal Medical Treatment of Difficult-to-treat Hypertension
Official title: Optimal Medical Treatment of Difficult-to-treat Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: National Institute of Cardiology, Warsaw, Poland
Sponsor class: OTHER
First posted: 2024-02-23
Enrollment: 2500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate best medical management to achieve the BP goals of ESC/ESH (120-129 / 70-79 mmHg) in HT patients who are \<65 years old and ineffectively treated (BP ≥ 130/80 mg) with 3 or more antihypertensive drugs

Detailed description: Purpose: To evaluate best medical management to achieve the ESC/ESH 2018 BP goals of 120-129 / 70-79 mmHg in HT patients aged \< 65 y not controlled on 3 or more antihypertensive drugs.

Study design:

Phase A (Active screening) (n = 2500) 7 days Confirmation of the true ineffectiveness of antihypertensive therapy based on 3 or more antihypertensive drugs (single or dual drug preparations) using ABPM and home BP measurements.

Phase B (Open-label, non-randomized) (n = 1250) 12 weeks Replacement of ineffective antihypertensive treatment based on 3 or more antihypertensive drugs (single or dual drug preparations) with a triple single pill combination (SPC) based on optimally combined antihypertensive drugs: perindopril + indapamide + amlodipine (P+I+A) or olmesartan + hydrocholothiazide + amlodipine (O+H+A).

Phase C (Double blind, randomized, parallel-group) (n = 480) 24 weeks

Comparison of antihypertensive efficacy and tolerability profile:

* spironolactone
* eplerenone
* torasemide attached as an antihypertensive drug of 4th choice.

Eligibility criteria: Inclusion Criteria:

* documented history of HT
* HT treated for at least six months,
* office BP ≥ 130 and / or ≥80 mm Hg (average seated BP at Visit 1)
* use of 3 or more antihypertensive drugs, including an ACEi/ARB and a thiazide/thiazide-like diuretic or loop diuretic (single drugs or double SPCs)
* stable antihypertensive treatment regimen - no changes in antihypertensive treatment strategy at least for 4 weeks
* able and willing to comply with all study procedures and able to attend one of the study centers

Exclusion Criteria:

* inability to give informed consent
* SBP ≥180 mm Hg and/or DBP ≥110 mm Hg and/or DBP \<60 mm Hg
* BMI ≥40 kg/m2
* eGFR of \<45 mL/min/1.73 m2
* potassium serum concentration \> 4.8 mmol/L or \< 3.5 mmol/L
* persistent hyponatremia or history of hyponatremia related to TD/TLD treatment (sodium concentration \<135 mmol/L)
* secondary hypertension (not including sleep apnea)
* chronic oral glucocorticoid therapy
* myocardial infarction or cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) in the year prior to study inclusion
* heart failure requiring treatment with diuretic or aldosterone antagonists
* cardiomyopathy exluding LVH related to HT
* severe valvular disease
* ascending aortic aneurysm ≥5 cm
* prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta blockers) for other chronic conditions (e.g. chronic coronary syndromes, arytmia) such that discontinuation might pose serious risk to health
* primary pulmonary hypertension
* decompensated hyperthyroidism or hypothyroidism
* severe liver dysfunction (alanine aminotransferase and/or asparagine aminotransferase activity ≥3 times the upper limit of normal value),
* documented contraindication or allergy to studied drugs
* limited life expectancy of \< 1 year at the discretion of the Investigator
* 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
* 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);
* concurrent enrollment in any other investigational drug or device trial
* anticipated change of medical status during the trial (e.g., surgical intervention requiring \>2 weeks convalescence)
* current therapy for cancer

Primary outcomes:
measure: Patients with uncontrolled BP on ABPM
timeFrame: First week of the patients' participation in the study
measure: Patients with controlled BP after 12 weeks on triple SPC
timeFrame: Next 12 weeks of the patients' participation in the study
measure: Systolic BP reduction on 4th antihypertensive drug
timeFrame: Last 24 weeks of the patients' participation in the study
Secondary outcomes:
measure: Percentage of patients with BP controlled confirmed by HBPM
timeFrame: First week of the patients' participation in the study
measure: Consistency of the rate of uncontrolled BP
timeFrame: First week of the patients' participation in the study
measure: Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by OBPM
timeFrame: Next 12 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by HBPM
timeFrame: Next 12 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by ABPM
timeFrame: Next 12 weeks of the patients' participation in the study
measure: Percentage of patients requiring an increase in the dose
timeFrame: Next 12 weeks of the patients' participation in the study
measure: Consistency of the rate of uncontrolled BP
timeFrame: Next 12 weeks of the patients' participation in the study
measure: The magnitude of the decrease in SBP and DBP on OBPM, ABPM and HBPM after 12 weeks
timeFrame: Next 12 weeks of the patients' participation in the study
measure: The magnitude of changes in HBPM and ABPM derived indices after 12 weeks
timeFrame: Next 12 weeks of the patients' participation in the study
measure: Phase C
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Changes of SBP on ABPM (24h mean) after 12 weeks of treatment
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by OBPM
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by HBPM
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by ABPM
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Phase C continuation
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Phase C continuation
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Changes in HBPM and ABPM derived indices after 12 weeks - comparison of treatment groups
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Changes of SBP on ABPM (24h mean) after 24 weeks of treatment compared against spironolactone
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Changes of SBP on ABPM (24h mean) after 24 weeks of treatment compared against baseline
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 24 weeks of treatment, confirmed by OBPM - comparison between groups
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 24 weeks of treatment, confirmed by HBPM - comparison between groups
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients with controlled BP after 24 weeks of treatment, confirmed by ABPM - comparison between groups
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Consistency of the rate of controlled BP between ABPM, HBPM and OBPM after 24 weeks
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Changes in SBP and DBP on OBPM, ABPM and HBPM after 24 weeks of treatment - comparison between groups
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Changes in HBPM and ABPM derived indices after 24 weeks of treatment - - comparison between groups
timeFrame: Last 24 weeks of the patients' participation in the study
measure: Percentage of patients requiring an increase in the dose of drugs used after 6 and 12 weeks - comparison between groups
timeFrame: Last 24 weeks of the patients' participation in the study
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: National Institute of Cardiology
state: Mazowieckie
Study officials:
affiliation: National Institute of Cardiology
name: Piotr Dobrowolski, Professor
role: PRINCIPAL_INVESTIGATOR
References: