Multi-center, Blinded, Randomized, Parallel-group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension (RHT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 730
- 试验地点
- 159
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
Participation in the study will be up to 68 weeks.
The study has 4 periods:
- Screening period
- Placebo run-in period
- Randomized treatment period
- Safety follow-up period
The screening period lasts between 4 and 12 weeks. It starts at the screening visit with the signing of the informed consent form (ICF) and ends the day before the participant enters the run-in period.
At least 4 weeks before the start of the run-in period, the background antihypertensive medication (except beta-blockers) of participants with a diagnosis of true resistant hypertension and having a mean trough sitting systolic blood pressure of equal to or greater than 140 mmHg measured by automated AOBPM will be standardized by switching to a fixed combination of a calcium channel blocker (amlodipine), an angiotensin receptor blocker (valsartan) and a diuretic (hydrochlorothiazide).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Aprocitentan 25 mg in Part 1 (double-blind)
Participants will receive aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
干预措施: Aprocitentan 25 mg (Drug)
Aprocitentan 12.5 mg in Part 1 (double-blind)
Participants will receive aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
干预措施: Aprocitentan 12.5 mg (Drug)
Placebo in Part 1 (double-blind)
Participants will receive placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
干预措施: Placebo (Drug)
Aprocitentan 25 mg in Part 2 (single-blind, single arm)
After 4-weeks in the double-blind randomized part (Part 1), participants will received 25 mg aprocitentan, orally, once daily in the morning for 32 weeks.
干预措施: Aprocitentan 25 mg (Drug)
Aprocitentan 25 mg in Part 3 (double-blind withdrawal)
After 32-weeks in the single-blind, single-arm part (Part 2), participants will be re-randomized and receive aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
干预措施: Aprocitentan 25 mg (Drug)
Placebo in Part 3 (double-blind withdrawal)
After 32-weeks in the single-blind, single-arm part (Part 2), participants will be re-randomized and receive placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
Changes from baseline to Week 4 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.
次要结局
- 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(Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40)
- 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(Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1))
- 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(Pre-dose Day 1 (Part 1 double-blind randomized baseline) and Week 4 (End of double-blind randomized part 1))
- 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(Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40)
- 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(From Week 36 (Part 3 double-blind-withdrawal baseline) and Week 40)