A research study to find out if aprocitentan is efficacious and safe to treat difficult to control (resistant) high blood pressure (hypertension)
- Conditions
- Resistant HypertensionMedDRA version: 21.1Level: LLTClassification code 10020783Term: Hypertension not adequately controlledSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2017-004393-33-NL
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
Screening criteria:
- Signed and dated ICF prior to any study-mandated procedure;
- Male and female subjects; 18 years (or year of country specific
majority) or older;
- Historical documentation in the subject's medical records on
uncontrolled BP despite at least 3 background antihypertensive
medications within 1 year before screening visit;
- Treated with at least 3 antihypertensive therapies of different
pharmacological classes for at least 4 weeks before the screening visit
(Visit 1);
- Mean SiSBP = 140 mmHg measured by AOBPM;
- Women of childbearing potential are eligible only if the following
applies;
-- Negative pregnancy test at screening and at baseline (i.e., end of RI
period);
-- Agreement to undertake pregnancy tests during the study and up to
30 days after randomized study treatment discontinuation;
-- Agreement to use methods of birth control from Screening up to at
least 30 days after randomized study treatment discontinuation.
Run-in entry criteria:
- Switched to the standardized background antihypertensive therapy at
least 4 weeks before the first RI visit;
- Mean trough SiSBP = 140 mmHg measured by AOBPM.
Randomization criteria:
- Stable dose of the standardized background antihypertensive therapy
for at least 1 week before Day -1 (end of the RI period);
- Mean trough SiSBP = 140 mmHg measured by AOBPM.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300
- Apparent/pseudo RHT due to white coat effect, medical inertia, poor
therapeutic adherence, or secondary causes of hypertension (except
sleep apnea);
- Confirmed severe hypertension (grade 3) defined as SiSBP = 180
mmHg and/or SiDBP = 110 mmHg as measured by AOBPM at two
different time points.;
- Pregnant or lactating subjects;
- Clinically significant unstable cardiac disease at screening or in the
past in the opinion of the investigator, e.g. uncontrolled symptomatic
arrhythmia, atrial fibrillation, congestive heart failure NYHA stage II
with relevant mitral valve insufficiency and/or aortic stenosis,
congestive heart failure NYHA stage III or IV;
- Severe renal insufficiency;
- N-terminal pro-brain natriuretic peptide (NT-proBNP) = 500 pg/mL;
- Any known factor, disease or clinically relevant medical or surgical
conditions that, in the opinion of the investigator, might put the subject
at risk, interfere with treatment compliance, study conduct or
interpretation of the results
- Treatment with any medication which may affect blood pressure
and/or treatment with high dose of loop diuretics (i.e., furosemide
greater than 80 mg/day, or equivalent dosage of other loop diuretics).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: From baseline to Week 4 after treatment initiation.;Main Objective: - To demonstrate the blood pressure (BP) lowering effect of aprocitentan when added to standard of care in true resistant hypertension (RHT) subjects.;Secondary Objective: - To demonstrate that the effect of aprocitentan on BP is durable when added to standard of care in true RHT subjects.<br><br>- To evaluate the long-term safety and tolerability of aprocitentan in true RHT subjects during 48 weeks of treatment.;Primary end point(s): - Change from baseline to Week 4 of double-blind (DB) treatment in mean trough SiSBP measured by AOBPM.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change from Week 36 (i.e., start of double-blind withdrawal [DB-WD]) to Week 40 in mean trough SiSBP measured by AOBPM<br>- Change from baseline to Week 4 of DB treatment in trough Sitting Diastolic BP (SiDBP) measured by AOBPM;<br>- Changes from baseline to Week 4 of DB treatment in 24-h mean SBP and DBP measured by ABPM;<br>- Change from Week 36 to Week 40 of DB-WD treatment in mean trough SiDBP measured by AOBPM;<br>- Changes from Week 36 to Week 40 of DB-WD treatment in 24-h mean SBP and DBP measured by ABPM.;Timepoint(s) of evaluation of this end point: From baseline to week 4, or from week 36 to week 40.