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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03541174




Registration number
NCT03541174
Ethics application status
Date submitted
17/05/2018
Date registered
30/05/2018

Titles & IDs
Public title
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
Scientific title
Multi-center, Blinded, Randomized, Parallel-group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension (RHT)
Secondary ID [1] 0 0
2017-004393-33
Secondary ID [2] 0 0
ID-080A301
Universal Trial Number (UTN)
Trial acronym
PRECISION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Resistant Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aprocitentan 12.5 mg
Treatment: Drugs - Aprocitentan 25 mg
Treatment: Drugs - Placebo

Experimental: Aprocitentan 25 mg in Part 1 (double-blind) - Participants will receive aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.

Experimental: 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.

Placebo comparator: Placebo in Part 1 (double-blind) - Participants will receive placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.

Experimental: 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.

Experimental: 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.

Placebo comparator: 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.


Treatment: Drugs: Aprocitentan 12.5 mg
Tablet, oral use

Treatment: Drugs: Aprocitentan 25 mg
Tablet, oral use

Treatment: Drugs: Placebo
Matching placebo tablet

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Pre-dose Day 1 (Part 1 double-blind randomized baseline) and Week 4 (End of double-blind randomized part 1)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
From Week 36 (Part 3 double-blind-withdrawal baseline) and Week 40

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Renal Research - Gosford
Recruitment hospital [2] 0 0
Westmead Hospital Department of Renal Medicine - Sydney
Recruitment hospital [3] 0 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment hospital [4] 0 0
Hypertension & Kidney Disease / Huma Neurotransmitter Laboratory - Melbourne
Recruitment hospital [5] 0 0
Curtin University, Faculty of Health Sciences, School of Public Health - Bentley
Recruitment hospital [6] 0 0
Royal Perth Hospital Unit - The University of Western Australia - Perth
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6102 - Bentley
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Idorsia Pharmaceuticals Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Janssen Biotech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Idorsia Pharmaceuticals Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Danaietash P, Verweij P, Wang JG, Dresser G, Kanto... [More Details]