INDAPAMIDE, AMLODIPINE BESILATE, PERINDOPRIL ARGININE for Hypertension

Inclusion criteria

• {"criterion_text":"- Women and men\n- Age: ≥18 years old, less than 75 years old\n- Documented history of HT\n- HT treated for at least six months\n- Office BP ≥ 130 and / or ≥80 mm Hg (average seated BP at Visit 1)\n- 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)\n- Stable antihypertensive treatment regimen – no changes in antihypertensive treatment strategy at least for 4 weeks\n- Able and willing to comply with all study procedures and able to attend one of the study centers"}

Exclusion criteria

• {"criterion_text":"- Inability to give informed consent\n- Office SBP ≥180 mm Hg and/or DBP ≥110 mm Hg and/or DBP <60 mm Hg\n- BMI ≥45 kg/m2\n- eGFR of <45 mL/min/1.73 m2\n- Potassium serum concentration > 5 mmol/L or < 3.5 mmol/L within the year prior to the screening visit\n- Persistent hyponatremia or history of hyponatremia related to TD/TLD treatment (sodium concentration <135 mmol/L)\n- Secondary or accelerated hypertension (not including sleep apnea)\n- Chronic glucocorticoid therapy\n- Myocardial infarction or cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) in the year prior to study inclusion\n- Heart failure with an ejection fraction ≤50%\n- Cardiomyopathy\n- Severe valvular disease\n- Aortic aneurysm\n- 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\n- Documented history of persistent or permanent atrial tachyarrhythmia requiring beta-blocker treatment\n- Primary pulmonary hypertension\n- Decompensated hyperthyroidism or hypothyroidism\n- Severe liver dysfunction (alanine aminotransferase and/or asparagine aminotransferase activity ≥3 times the upper limit of normal value)\n- Documented contraindication or allergy to studied drugs\n- Limited life expectancy of < 1 year at the discretion of the Investigator\n- 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\n- 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);\n- Concurrent enrollment in any other investigational drug or device trial\n- Anticipated change of medical status during the trial (e.g., surgical intervention requiring >2 weeks convalescence)\n- Current therapy for cancer"}

Primary endpoints

• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Measured by ABPM (24h mean SBP and DBP); uncontrolled BP defined as 24h mean SBP ≥125 mm Hg or 24h mean DBP ≥80 mm Hg; analysis in ITT-A dataset."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Measured by ABPM (24h mean SBP and DBP) at Visit 5 (after 12 weeks). BP control defined as 24h mean SBP <125 mm Hg and 24h mean DBP <80 mm Hg; analysis in ITT-B dataset."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Change from baseline to week 12 in mean 24h SBP measured by ABPM; primary analysis on per-protocol (PP) set; ABPM after premature discontinuation excluded."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Measured by HBPM (home blood pressure monitoring) mean over 6 days; threshold SBP ≥130 mm Hg or DBP ≥80 mm Hg for Phase A secondary endpoint."}
• {"endpoint_text":"- Phase A: - Consistency of the rate of uncontrolled BP between ABPM and HBPM","definition_or_measurement_approach":"Comparison/consistency assessment between ABPM (24h mean) and HBPM measurements."}

Methods

• Site-based recruitment at participating clinical centres in Poland (multiple hospital and clinic sites listed in trial sites).
• Information leaflet (document: K2_Recruitment material Information leaflet) provided to potential participants.
• Posters (document: K2_Recruitment material Poster) for recruitment.
• Social media posts (document: K2_Recruitment material Social Media Posts) — digital outreach.
• Recruitment spot transcripts for investigators and participants (documents: K2_Recruitment materials_spot transcription_investigators and _participants).

Poland

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

483

Number Of Sites

20

Number Of Participants

1154

Primary sponsor

Full Name

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Poland

Third parties

• {"country":"Poland","full_name":"Zakład Biologii Medycznej, Biobank, Pracownia Spektrometrii Mas.","duties_or_roles":"Central lab testing","organisation_type":"Educational Institution"}
• {"country":"Poland","full_name":"Scientia Research Institute Sp. z o.o.","duties_or_roles":"Sponsor duties codes: 1, 11, 12, 8, 9 (as provided in submission)","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"DiCELLA","duties_or_roles":"Sponsor duties code: 7 (as provided in submission)","organisation_type":"Educational Institution"}
• {"country":"Poland","full_name":"Cefea Sp. z o.o. sp.k.","duties_or_roles":"Packaging, labeling, and delivery of the IMP, IMP release","organisation_type":"Pharmaceutical company"}