Phase 3 N=730 Randomized Triple-blind Treatment

A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety

Resistant Hypertension

Bottom Line

View on ClinicalTrials.gov: NCT03541174 ↗

Enrolled (actual)

730

Serious AEs

6.3%

Results posted

Mar 2023

Primary outcome: Primary: Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Automated Office Blood Pressure Measurement — -15.26; -15.20; -11.47 mmHg — p=0.0042

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Aprocitentan 12.5 mg (Drug); Aprocitentan 25 mg (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Idorsia Pharmaceuticals Ltd.
Primary completion: May 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Automated Office Blood Pressure Measurement	-15.26; -15.20; -11.47	0.0042 sig
SECONDARY Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Unattended Automated Office Blood Pressure Measurement	-1.47; 4.36	<0.0001 sig
SECONDARY Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure Measurement	-10.43; -10.95; -6.48	<0.0001 sig
SECONDARY Changes From Baseline to Week 4 of Double-blind Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring	-6.73; -8.44; -2.55; -6.25; -7.74; -1.92	<0.0001 sig
SECONDARY Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure	-0.52; 4.67	<0.0001 sig
SECONDARY Changes From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring	-0.07; 6.46; -0.47; 6.28	<0.0001 sig

Summary

The goal of this clinical trial is to show the blood pressure lowering effect of aprocitentan, a new drug, when added to other anti-hypertensive drugs of patients with difficult to control (resistant) high blood pressure (hypertension), and to show that blood pressure reduction is kept for long period of time.

Eligibility Criteria

Inclusion Criteria

Screening period:

Signed and dated informed consent form (ICF) prior to any study-mandated procedure;
Male and female participants; 18 years (or year of country specific majority) or older;
Historical documentation in the participant's medical records on uncontrolled blood pressure 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 Sitting Systolic Blood Pressure (SiSBP) greater or equal to 140 mmHg measured by Automated Office Blood Pressure Measurement (AOBPM);
Women of childbearing potential are eligible only if the following applies:
Negative pregnancy test at screening and at baseline (i.e., before randomization);
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 period (RI):

Switched to the standardized background antihypertensive therapy at least 4 weeks before the first RI visit;
Mean trough SiSBP greater than or equal to140 mmHg as measured by AOBPM.

Randomization period:

Stable dose of the standardized background antihypertensive therapy for at least 1 week before the end of the RI period;
Mean trough SiSBP greater than or equal to 140 mmHg measured by AOBPM.

Exclusion Criteria

Apparent/pseudo Resistant Hypertension (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 greater than or equal to 180 mmHg and/or Sitting Diastolic Blood Pressure (SiDBP) greater than or equal to 110 mmHg as measured by AOBPM at two different timepoints;
Pregnant or lactating participants;
Clinically significant unstable cardiac disease at screening or in the past in the opinion of the investigator (exclusion of participants with significant or potential unstable cardiac disease);
Severe renal insufficiency;
Any known factor, disease or clinically relevant medical or surgical conditions that, in the opinion of the investigator, might put the participant at risk, interfere with treatment compliance, study conduct or interpretation of the results.
Treatment with any medication which may affect blood pressure (BP) and/or treatment with high dose of loop diuretics (i.e., furosemide greater than 80 mg/day, or equivalent dosage of other loop diuretics).

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03541174). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.