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
- Conditions
- Resistant Hypertension
- Interventions
- Registration Number
- NCT03541174
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- Brief 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.
- Detailed Description
Participation in the study will be up to 68 weeks.
The study has 4 periods:
1. Screening period
2. Placebo run-in period
3. Randomized treatment period
4. 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).
In case a beta-blocker is used as one of the background antihypertensive medications or for any other indication, this can be kept, with the provision that it has been initiated and the dose kept stable for at least 4 weeks prior to the screening visit and the dose kept stable until the end-of-treatment.
Following the screening period this study has a run-in period of 4 weeks. During this period, placebo will be administered in order to exclude potential placebo responders.
Following the run-in period eligible participants will enter the randomized treatment period. This period lasts for 48 weeks. It starts at randomization (i.e., Day 1 of the double-blind part) and ends at the end-of-treatment visit (i.e., at the end of the double-blind withdrawal part).
The randomized treatment period consists of 3 parts: Part 1 is double-blind, randomized, parallel-group and placebo-controlled and lasts 4 weeks. Part 2 is single-blind and single-arm and lasts for 32 weeks. Part 3 is a double-blind withdrawal, randomized, parallel-group and placebo-controlled and lasts for 12 weeks.
End-of treatment is at Week 48 (i.e., end of the double-blind withdrawal part). The safety follow-up starts on the day after the last dose of study treatment and ends 30 to 33 days after the last dose of study treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 730
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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aprocitentan 25 mg in Part 3 (double-blind withdrawal) Aprocitentan 25 mg 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 in Part 3 (double-blind withdrawal) Placebo 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. Aprocitentan 25 mg in Part 1 (double-blind) Aprocitentan 25 mg Participants will receive aprocitentan 25 mg, orally, once daily in the morning for 4 weeks. Aprocitentan 12.5 mg in Part 1 (double-blind) Aprocitentan 12.5 mg Participants will receive aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks. Placebo in Part 1 (double-blind) Placebo Participants will receive placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks. Aprocitentan 25 mg in Part 2 (single-blind, single arm) Aprocitentan 25 mg 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.
- Primary Outcome Measures
Name Time Method 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 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.
- Secondary Outcome Measures
Name Time Method 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 Changes from double-blind withdrawal baseline (Week 36) to Week 40 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.
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 in mean trough SiDBP 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. 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). The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. A negative change indicates a decrease in SiDBP from baseline.
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) ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (baseline and Week 4) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve and divided by the time span. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.
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 (Week 36) to Week 40 in mean trough SiDBP 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 SiDBP from baseline.
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 ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (the double-blind withdrawal baseline \[Week 36\] and the week 40) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.
Trial Locations
- Locations (159)
TLM Medical Services LLC
🇺🇸Columbia, South Carolina, United States
Academic Medical Research Institute Inc
🇺🇸Los Angeles, California, United States
California Kidney Specialists
🇺🇸San Dimas, California, United States
Midwest Institute for Clinical Research
🇺🇸Indianapolis, Indiana, United States
University Hospitals Cleveland Medical Center - Neurological Institute
🇺🇸Cleveland, Ohio, United States
Canadian Phase Onward Inc.
🇨🇦Toronto, Ontario, Canada
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Advanced Cardiovascular, LLC
🇺🇸Alexander City, Alabama, United States
Medycyna Kliniczna
🇵🇱Warszawa, Poland
Curtin University, Faculty of Health Sciences, School of Public Health
🇦🇺Bentley, Western Australia, Australia
Interni oddeleni, Nefrologie
🇨🇿Prague, Czechia
Všeobecní fakultní nemocnice Praha
🇨🇿Praha 2, Czechia
Universitair Ziekenhuis Gent Cardiologie
🇧🇪Gent, Belgium
Maastricht University Medical Center, Dept. of Medicine
🇳🇱Maastricht, Netherlands
Azienda Ospedaliero Universitaria Pisana - Department Clinical and Experimental Medicine
🇮🇹Pisa, Italy
Burke Internal Medicine & Research
🇺🇸Burke, Virginia, United States
Clinic of Cardiology and Rehabilitation
🇱🇹Klaipeda, Lithuania
ETG Lublin
🇵🇱Lublin, Poland
Hospital Erasme - Cardiology department
🇧🇪Brussels, Belgium
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
State Budgetary Healthcare Institution of Arkhangelsk Region "First City Clinical Hospital n.a. E.E. Volosevich"
🇷🇺Arkhangelsk, Russian Federation
Centre Hospitalier Universitaire du Sart-Tilman
🇧🇪Liège, Belgium
SCU Medicina Interna e Centro Ipertensione arteriosa. Dipartimento di Scienze Mediche Università di Torino, Aou Citta' Salute E Scienza Torino
🇮🇹Torino, Italy
Renal Research
🇦🇺Gosford, New South Wales, Australia
Clinical Research Solutions Inc.
🇨🇦Waterloo, Ontario, Canada
ETG Zgierz
🇵🇱Zgierz, Poland
University Brescia Department Clinical and Experimental Science
🇮🇹Brescia, Italy
Academic Medical Center Amsterdam
🇳🇱Amsterdam, Netherlands
Zuyderland Medical Center
🇳🇱Geleen, Netherlands
Etyka Ośrodek Badań Klinicznych
🇵🇱Olsztyn, Poland
Baker Heart and Diabetes Institute
🇦🇺Melbourne, Victoria, Australia
Royal Perth Hospital Unit - The University of Western Australia
🇦🇺Perth, Western Australia, Australia
ETG Warszawa
🇵🇱Warszawa, Poland
Fundació Puigvert
🇪🇸Barcelona, Spain
Diamond Clinic
🇵🇱Kraków, Poland
Hospital Clinico San Carlos - Istituto de Investigacion Sanitaria San Carlos (IdISSC)
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
O.F. Herbachevsky Zhytomyr Regional Clinical Hospital, Cardiology department
🇺🇦Zhytomyr, Ukraine
Haemek Medical Center
🇮🇱Afula, Israel
Hospital Clínic Universitari de València
🇪🇸Valencia, Spain
Hospital Vall d'Hebron de Barcelona
🇪🇸Barcelona, Spain
Kyiv Municipal Clinical Emergency Hospital
🇺🇦Kyiv, Ukraine
Federal State Budget Scientific Institution "Scientific Research Institute for Complex Issues of Cardiovascular Diseases"
🇷🇺Kemerovo, Russian Federation
Hospital Virgen de las Nieves - Internal Medicine Department
🇪🇸Granada, Spain
Hospital Virgen del Rocio Departamento de Medicina Interna
🇪🇸Sevilla, Spain
National Medical Research Center for Preventive Medicine
🇷🇺Moscow, Russian Federation
Federal State Military Educational Institution of Higher Professional Education, Military Medical Academy named for S. M. Kirov of the Ministry of Defense of the Russian Federation
🇷🇺Saint Petersburg, Russian Federation
Kyiv City Clinical Hospital # 1
🇺🇦Kyiv, Ukraine
State Institution "National Scientific Center "M.D. Strazhesko Institute of Cardiology" of the National Academy of Medical Sciences of Ukraine"
🇺🇦Kyiv, Ukraine
Volyn Regional Center for Cardiovascular Pathology, Rehabilitation Department
🇺🇦Lutsk, Ukraine
Federal State Budget Scientific Institution "Tomsk National Research Medical Center of the Russian Academy of Sciences"
🇷🇺Tomsk, Russian Federation
State Institution "L.T. Malaya Therapy National Institute of the NAMS of Ukraine"
🇺🇦Kharkiv, Ukraine
State Institution "Institute of Gerontology named after D.F. Chebotarev of National Academy of Medical Sciences of Ukraine"
🇺🇦Kyiv, Ukraine
Federal State Budget Institution National Medical Research Center n.a. V.A. Almazov of the Ministry of Healthcare of the Russia
🇷🇺Saint Petersburg, Russian Federation
Municipal non-profit enterprise "Clinical Hospital # 8"of Kharkiv City Council
🇺🇦Kharkiv, Ukraine
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Queen Mary University of London
🇬🇧London, United Kingdom
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, China
Zhejiang Province People's Hospital
🇨🇳Hangzhou, China
Ruijin Hospital Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
Scientific Research Institute - Regional Clinical Hospital №1
🇷🇺Krasnodar, Russian Federation
State budget healthcare institution of Novosibirsk region "City clinical hospital #34"
🇷🇺Novosibirsk, Russian Federation
Federal State Budget Institution "National Medical Research Center n.a. V.A. Almazov" of the Ministry of healthcare of the Russian Federation
🇷🇺St. Petersburg, Russian Federation
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Science
🇷🇺Tyumen, Russian Federation
Clinical Trials Research
🇺🇸Lincoln, California, United States
Amicis Research Center
🇺🇸Northridge, California, United States
Canvas Clinical Research, LLC
🇺🇸Lake Worth, Florida, United States
Grace Research, LLC
🇺🇸Bossier City, Louisiana, United States
Hypertension and Nephrology Association PA
🇺🇸Eatontown, New Jersey, United States
MedStar Health Research Institute
🇺🇸Hyattsville, Maryland, United States
Great Lakes Medical Research LLC
🇺🇸Westfield, New York, United States
Physician's East Endocrinology
🇺🇸Greenville, North Carolina, United States
Stern Cardiovascular Foundation, Inc
🇺🇸Germantown, Tennessee, United States
Amarillo Heart Clinical Research Institute, Inc.
🇺🇸Amarillo, Texas, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Hypertension & Kidney Disease / Huma Neurotransmitter Laboratory
🇦🇺Melbourne, Victoria, Australia
Clinique Universitaires de Saint Luc, Departement cardio-vasculaires intensives
🇧🇪Brussels, Belgium
The First Affiliated Hospital of Baotou Medical College of Inner Mongolia
🇨🇳Baotou, China
Guangdong General Hospital
🇨🇳Guangzhou, China
Hainan NO.3 Provincial people's Hospital
🇨🇳Sanya, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, China
FN U Sv.Anny Brno, kardiologická klinika
🇨🇿Brno, Czechia
Thomayerova nemocnice
🇨🇿Praha 4, Czechia
Kardio Václavík s.r.o
🇨🇿Přerov, Czechia
Centre Hospitalier Intercommunal Toulon La Seyne sur Mer
🇫🇷Toulon, France
Universitätsklinikum Nürnberg Süd
🇩🇪Nürnberg, Germany
General Hospital of Athens, Ippokrateio
🇬🇷Athens, Greece
General Hospital of Athens Georgios Gennimatas
🇬🇷Athens, Greece
Asklepeion General Hospital
🇬🇷Athens, Greece
General Hospital Konstantopouleio-Patision
🇬🇷Nea Ionia, Greece
DRC Gyógyszervizsgáló Központ Kft.
🇭🇺Balatonfüred, Hungary
Gottsegen György Országos Kardiológiai Intézet
🇭🇺Budapest, Hungary
Debreceni Egyetem - Klinikai Központ
🇭🇺Debrecen, Hungary
Galilee Medical Center
🇮🇱Nahariya, Israel
Ospedale San Gerardo, Clinica Medica
🇮🇹Monza, Italy
Azienda Ospedaliera S. Andrea di Roma - Division of Cardiology and of Cardiothoracic and Vascular Science Department -
🇮🇹Roma, Italy
Uniwersyteckie Centrum Kliniczne Centrum Kardiologii
🇵🇱Gdańsk, Poland
KO-MED. Centra Kliniczne Sp. Z o.o. Ośrodek Badań Klinicznych w Puławach
🇵🇱Puławy, Poland
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
🇵🇱Warszawa, Poland
Klinika Wad Wrodzonych Serca Instytut Kardiologii im. Kardynala Wyszynskiego
🇵🇱Warszawa, Poland
Samodzielny Publiczny Szpital Wojewódzki im. Papieża Jana Pawła II w Zamościu
🇵🇱Zamość, Poland
Federal State Autonomous Institution of Higher Education "Kazan (Volga Region) Federal University"
🇷🇺Kazan, Russian Federation
State Budgetary Educational Institution of Higher Professional Education Smolensk State Medical Academy
🇷🇺Smolensk, Russian Federation
State Healthcare Institution "Regional Clinical Cardiology Dispensary"
🇷🇺Saratov, Russian Federation
Hospital del Mar
🇪🇸Barcelona, Spain
State Institution "D.F. Chebotarev Institute of Gerontology, National Academy of Medical Science of Ukraine"
🇺🇦Kyiv, Ukraine
Danylo Halytsky Lviv National Medical University
🇺🇦Lviv, Ukraine
Communal Non-profit Enterprise "Vinnytsya regional Clinical Hospital named after. N.I. Pirogov Vinnytsia Regional Council"/ National Pirogov Memorial Medical University, Vinnytsya
🇺🇦Vinnytsya, Ukraine
SIU School of Medicine Center for Clinical Research
🇺🇸Springfield, Illinois, United States
Century Clinical Research, Inc
🇺🇸Daytona Beach, Florida, United States
Chrishard Medical Group
🇺🇸Inglewood, California, United States
Bay Area Cardiology Associates, P.A.
🇺🇸Brandon, Florida, United States
East Coast Institute for Research
🇺🇸Saint Augustine, Florida, United States
Premier Medical Associates
🇺🇸The Villages, Florida, United States
Scott Research Inc
🇺🇸Laurelton, New York, United States
Clinical Research Consultants, LLC
🇺🇸Kansas City, Missouri, United States
Cardiovascular Research of Northwest Indiana, L.L.C.
🇺🇸Munster, Indiana, United States
Metrolina Internal Medicine/Internal Medicine Research
🇺🇸Charlotte, North Carolina, United States
Renal Medicine Associates
🇺🇸Albuquerque, New Mexico, United States
Reid Physician Associates
🇺🇸Richmond, Indiana, United States
Milwaukee Nephrologists, SC
🇺🇸Wauwatosa, Wisconsin, United States
Carteret Medical Group
🇺🇸Morehead City, North Carolina, United States
DeGarmo Institute of Medical Research
🇺🇸Greer, South Carolina, United States
Willamette Valley Clinical Studies
🇺🇸Eugene, Oregon, United States
LinQ Research, LLC
🇺🇸Pearland, Texas, United States
Universitätsklinikum des Saarlandes
🇩🇪Homburg/Saar, Germany
LifeDOC Research PLLC
🇺🇸Memphis, Tennessee, United States
Manna Research Inc (North Burlington)
🇨🇦Hamilton, Ontario, Canada
Herzzentrum Leipzig Universitätsklinik für Kardiologie
🇩🇪Leipzig, Germany
London Health Sciences Centre - Victoria Hospital
🇨🇦London, Ontario, Canada
Mercury Clinical Research
🇺🇸Webster, Texas, United States
St. George Kidney Care LLC dba Southern Utah Kidney and Hypertension Center
🇺🇸Saint George, Utah, United States
Westmead Hospital Department of Renal Medicine
🇦🇺Sydney, New South Wales, Australia
Hôpital Européen Georges Pompidou- Centre d' Investigation Clinique
🇫🇷Paris, France
Universitätsklinikum Düsseldorf Klinik für Nephrologie
🇩🇪Düsseldorf, Germany
Stephen S. Chow Medicine Professional Corporation
🇨🇦Toronto, Ontario, Canada
Federal State Budget Educational Institution of Higher Education "Saratov State Medical University n.a. V.I. Razumovskiy" of the Ministry of Healthcare of the Russian Federation
🇷🇺Saratov, Russian Federation
Jewish Hospital Berlin
🇩🇪Berlin, Germany
CHU Grenoble - Alpes
🇫🇷Grenoble cedex 9, France
Hôpital de la Croix-Rousse - Rhône
🇫🇷Lyon, France
Universitätsklinikum Erlangen Klinische Forschungsstation (CRC)
🇩🇪Erlangen, Germany
Hypertension Clinic, Internal Medicine, Hospital Clinico, University of Valencia, Valencia
🇪🇸Valencia, Spain
Barzilai Medical Center, Cardiovascular Institute
🇮🇱Ashkelon, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Markusovszky Egyetemi Oktatókórház
🇭🇺Szombathely, Hungary
Aberdeen Royal Infirmary, Clinical Pharmacology Unit
🇬🇧Aberdeen, United Kingdom
Federal State Budget Scientific Institution "Federal Research Center Institute of Cytology and Genetics of Siberian Department of Russian Academy of Sciences"
🇷🇺Novosibirsk, Russian Federation
Clinical Research Centre The University of Edinburgh Centre for Cardiovascular Science
🇬🇧Edinburgh, United Kingdom
University of Oulu, Medical Research Center
🇫🇮Oulu, Finland
JSC "InMedica"
🇱🇹Kaunas, Lithuania
SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi
🇵🇱Lodz, Poland
Sheba Medical Center
🇮🇱Tel HaShomer, Israel
East Carolina University
🇺🇸Greenville, North Carolina, United States
TAYS RDI center (Tampere University Hospital,Specialist Internal Medicine, Rare Diseases)
🇫🇮Tampere, Finland
Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mielęckiego Śląskiego Uniwersytetu Medycznego w Katowicach
🇵🇱Katowice, Poland
KO-MED. CentraKliniczne Sp. Z o.o. Ośrodek Badań Klinicznych w Lublinie II
🇵🇱Lublin, Poland
ETG Skierniewice
🇵🇱Skierniewice, Poland
Turku University Central Hospital - Turun yliopistollinen keskussairaala Sisätautien klinikka
🇫🇮Turku, Finland
Albany Medical College
🇺🇸Albany, New York, United States