Clinical trial NCT05196035: A Study to Learn More About How Well the Study Treatment Finerenone Works, How Safe it is, How it Moves Into, Through, and Out of the Body, and the Effects it Has on the Body When Taken With an ACE Inhibitor or Angiotensin Receptor Blocker in Children With Chronic Kidney Disease and Proteinuria
Official title: A 6-month Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and PK/PD of an age-and Body Weight-adjusted Oral Finerenone Regimen, in Addition to an ACEI or ARB, for the Treatment of Children, 6 Months to <18 Years of Age, With Chronic Kidney Disease and Proteinuria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Kidney Disease
Proteinuria
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2022-01-19
Enrollment: 219
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers are looking for a better way to treat children who have chronic kidney disease (CKD), which is long-term kidney disease, and proteinuria, a condition in which a person´s kidneys leak protein into the urine.

The kidneys filter waste and fluid from the blood to form urine. In children with CKD, the kidney´s filters do not work as well as they should. This can lead to accumulation of waste and fluid in the body and proteinuria. CKD can lead to other medical problems, such as high blood pressure, also known as hypertension. Vice versa, hypertension and proteinuria can also contribute to worsening of CKD. Therefore, the treatment of CKD aims to control blood pressure and proteinuria. There are treatments available for doctors to prescribe to children with CKD and hypertension and/or proteinuria. These include "angiotensin-converting enzyme inhibitors" (ACEI) and "angiotensin receptor blockers" (ARB). Both ACEI and ARB can improve kidney function by helping the renin-angiotensin-aldosterone system (RAAS) to work normally. The RAAS is a system that works with the kidneys to control blood pressure and the balance of fluid and electrolytes in the blood. In people with CKD, the RAAS is often too active, which can stop the kidneys from working properly and cause hypertension and proteinuria. However, ACEI or ARB treatment alone does not work for all patients with CKD as they only target the angiotensin part of the renin-angiotensin-aldosterone system.

The study treatment, finerenone, is expected to help control RAAS overactivation together with an ACEI or ARB.

So, the researchers in this study want to learn more about whether finerenone given in addition to either an ACEI or ARB can help their kidney function.

The main purpose of this study is to learn more about whether finerenone added to either ACEI or ARB can help reduce the amount of protein in the participants' urine more than a placebo. A placebo looks like a treatment but does not have any medicine in it. Participants will also continue to receive their other medications.

To see how the treatment work, the doctors will take samples of the participants' urine to measure their protein levels before and during taking treatment and after their last treatment. In addition, blood samples will be taken to monitor kidney function, electrolytes and the amount of finerenone in the blood as well as for other tests.

This study will include children with CKD and proteinuria aged from 6 months up to less than 18 years. The participants will take:

* either finerenone or the placebo, in addition to
* either ACEI or ARB, whichever they take as part of their normal treatment

Two visits are required up to 104 days, to check whether a child can take part in the treatment phase of the study. If participants qualify for the treatment phase, they will then undergo treatment for about 180 days. During this time, they will visit the study site at least 7 times. During these visits, the participants will:

* have their blood pressure, heart rate, temperature, height and weight measured
* have blood and urine samples taken
* have physical examinations
* have their heart examined by an electrocardiogram and echocardiography (a sonogram of the heart)
* answer questions about their medication and whether they have any adverse events , or have their parents or guardians answer
* answer questions about how they are feeling, or have their parents or guardians answer
* answer question about how they like the study medication, or have their parents or guardians answer

The doctors will keep track of any adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

The doctors will check the participants' health about 30 days after the participants take their last treatment.


Eligibility criteria: Inclusion Criteria:

* Participants must be 6 months to \<18 years old at the time when the informed consent/assent is signed
* Participants must have a clinical diagnosis of chronic kidney disease (CKD) at screening which is defined as

  * CKD stages 1-3 (eGFR ≥30 mL/min/1.73m\^2) for children ≥1 year to \<18 years of age or
  * a serum creatinine ≤ 0.40 mg/dL for infants 6 months to \< 1 year of age and
  * severely increased proteinuria as defined by

    * Urinary protein-to-creatinine ratio (UPCR) of ≥ 0.50 g/g in participants ≥ 2 years with CKD stage 2 and 3 or
    * UPCR ≥ 1.0 g/g for patients \< 2 years of age or ≥ 2 years of age and with CKD stage 1
* Participants must have stable kidney function between screening and D0 defined as:

  * For participants with a creatinine of \> 0.8 mg/dL at screening: no increase or decrease in eGFR by ≥ 20% at D0
  * For participants with a creatinine of ≤ 0.8 mg/dL at screening: no increase or decrease in creatinine ≥ 0.15 mg/dL at D0.
* Treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at optimized doses defined as maximally tolerable doses within the recommended dose range according to guidelines on blood pressure management, unchanged for at least 30 days prior to screening
* K+ ≤5.0 mmol/L for children ≥2 years of age at both screening and D0, and ≤5.3 mmol/L for children \<2 years of age at both screening and D0

Exclusion Criteria:

* Planned urological surgery expected to influence renal function
* Children with hemolytic uremic syndrome (HUS) diagnosed ≤6 months prior to screening
* Patients with nephrotic syndrome receiving albumin infusions within the last 6 months prior to screening
* Patients who are candidates for renal transplantation, i.e., a kidney transplantation scheduled within the study time frame
* Renal allograft in place
* Bilateral renal artery stenosis
* Acute kidney injury requiring dialysis within 6 months prior to screening
* Systemic hypertension stage 2 in children ≥1 year of age defined according to guidelines on blood pressure management at screening or randomization
* Systolic blood pressure (SBP) above 110 mmHg in infants 6 months to \<1 year of age at screening or randomization
* Systemic hypotension defined as a systolic blood pressure below the 5th percentile for age, sex and height at either screening or randomization but no lower than 80 mmHg (although for some participants the 5th percentile of SBP is \< 80 mmHg they must be excluded if their SBP is \<80 mmHg)
* Participants with immune-mediated CKD using rituximab, cyclophosphamide, abatacept, or high-dose glucocorticoids, within \<6 months prior to screening

Primary outcomes:
measure: Urinary protein-to-creatinine ratio (UPCR) reduction of at least 30% from baseline to day 180±7
timeFrame: From baseline to day 180±7
Secondary outcomes:
measure: Number participants with treatment emergent adverse events (TEAEs）
timeFrame: From the start of study intervention to last study intervention + 3 days (up to 190 days)
measure: Change in serum potassium levels from baseline to day 180±7
timeFrame: From baseline to day 180±7
measure: Change in serum creatinine from baseline to day 180±7
timeFrame: From baseline to day 180±7
measure: Change in eGFR from baseline to day 180±7
timeFrame: From baseline to day 180±7
measure: Change in systolic blood pressure from baseline to day 180±7
timeFrame: From baseline to day 180±7
measure: Mean reduction from baseline to day 180±7 in UPCR
timeFrame: From baseline to day 180±7
measure: Change in UACR from baseline to day 180±7
timeFrame: From baseline to day 180±7
measure: Pharmacokinetics (PK) finerenone Cmax, md
timeFrame: Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7
measure: Pharmacokinetics (PK) finerenone AUCτ,md
timeFrame: Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7
measure: Taste and texture questionnaire of the pediatric formulation
timeFrame: On day 30±3 and day 180±7
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital | Main - Transplant Department
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Palo Alto
country: United States
facility: Lucille Packard Children's Hospital Stanford - Pediatric Nephrology
state: California
city: Washington
country: United States
facility: Children's National Medical Center - Nephrology
state: District of Columbia
city: Hollywood
country: United States
facility: South Broward Hosp. District dba Memorial Healthcare System
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital/Children's Healthcare of Atlanta - Nephrology
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: The Charlotte R. Bloomberg Children's Center Building - Nephrology
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital - Main Campus - Nephrology
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital Kansas City - Nephrology
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center | Division of Nephrology and Hypertension
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic | Pediatric Nephrology
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital - Nephrology
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science Univ | Doernbecher Childrens Hosp
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Nephrology
state: Pennsylvania
city: San Antonio
country: United States
facility: Univ of Texas Health Science Center | Nephrology Res Dept
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Instituto Universitario Hospital Italiano de Buenos Aires | Hospital Italiano de Buenos Aires - Neurology Department
state: Ciudad Auton. De Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital General de Ninos Ricardo Gutierrez | Pediatric Nephrology Department
state: Ciudad Auton. De Buenos Aires
city: San Luis
country: Argentina
facility: Centro de Rehabilitacion Cardiovascular | San Luis, Argentina
state: Provincia De San Luis
city: Santa Fe
country: Argentina
facility: Clinica de Nefrologia, Urologia y Enfermedades Cardiovascualares | Santa Fe, Argentina
state: Provincia De Santa Fe
city: Buenos Aires
country: Argentina
facility: Hospital de Pediatría Juan P. Garrahan
city: Buenos Aires
country: Argentina
facility: Hospital General de Ninos Pedro de Elizalde | Nephrology Department
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital Melbourne
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Campus IV
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Univ Graz | Kinder & Jugendheilkunde
state: Steiermark
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg - Landeskrankenhaus
city: Wien
country: Austria
facility: AKH Wien | Kinder & Jugendheilkunde, Kindernephrologie
city: Bruxelles - Brussel
country: Belgium
facility: Huderf / Ukzkf
city: Bruxelles - Brussel
country: Belgium
facility: CU Saint-Luc/UZ St-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg - Pediatric Nephrology
city: Liège
country: Belgium
facility: CHC Montlégia - Pediatrics
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de Belo Horizonte
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe
state: Parana
city: Ribeirão Preto/SP
country: Brazil
facility: Hosp Clínicas Facult. Med. de Ribeirão Preto / USP
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital PUC-Campinas | Centro de Pesquisa Clínica Sao Lucas
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Infantil Sabará - Instituto PENSI - Pesquisa e Ensino em Saúde Infantil
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto da Crianca e do Adolescente
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi
city: Sofia
country: Bulgaria
facility: SHATPD "Prof. Ivan Mitev"
city: Stara Zagora
country: Bulgaria
facility: MHAT prof. Stoyan Kirkovitch AD
city: Calgary
country: Canada
facility: Alberta Children's Hospital - Nephrology Clinic
state: Alberta
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children (SickKids)
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Børn og Unge
city: Odense C
country: Denmark
facility: Odense Universitetshospital - HC Andersen Børne og Ungehospital
city: Århus N
country: Denmark
facility: Aarhus Universitetshospital - Børn og Unge
city: Helsinki
country: Finland
facility: Helsinki University Hospital | Children's Hospital - Clinical Trial Unit, Nephrology Department
city: Tampere
country: Finland
facility: Tays Service Centre | Tampere University Hospital - Pediatric Early Phase Clinical Trials Unit
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: BORDEAUX cedex
country: France
facility: Hôpital Pellegrin - Bordeaux
city: Bron
country: France
facility: CHU de Lyon - Hopital Femme Mère Enfant
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve CHU Montpellier
city: Paris
country: France
facility: Hopital Robert Debre
city: Strasbourg
country: France
facility: CHU Strasbourg - Hopital Hautepierre
city: TOULOUSE Cedex 9
country: France
facility: Hôpital des Enfants
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
state: Niedersachsen
city: Bonn
country: Germany
facility: Kindernierenzentrum Bonn
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitaetsklinikum Muenster
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité / Pädiatrie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf (UKE)
city: Athens
country: Greece
facility: Children's Hospital of Athens Agia Sofia - Pediatric Nephrology Department
city: Athens
country: Greece
facility: Children's Hospital of Athens P&A Kyriakou - Pediatric Nephrology Department
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion - Department of Paediatrics
city: Ioannina
country: Greece
facility: Univ. General Hospital of Ioannina - Department of Paediatrics, Nephrology Unit
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki - 3rd Department of Paediatrics, Nephrology Unit'
city: Budapest
country: Hungary
facility: Semmelweis University
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
city: Bangalore
country: India
facility: St. John's National Academy of Health Sciences
city: Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS) - New Delhi
city: Kolkata
country: India
facility: NRS Medical college
city: Beer Sheva
country: Israel
facility: Clalit Health | Soroka Medical Center - Internal Medicine Department
city: Jerusalem
country: Israel
facility: Wilf Children's Hospital Shaare Zedek Medical Center
city: Nahariya
country: Israel
facility: Health Corporation of Galilee Medical Center
city: Petach Tikva
country: Israel
facility: Clalit Health Services Schneider Children's Medical Center
city: Tel Aviv
country: Israel
facility: Dana-Dwek Children's Hospital
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola - Pediatria
state: Emilia-Romagna
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - Nefrologia
state: Lazio
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini - Nefrologia e Trapianto Rene
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Nefrologia e Dialisi Pediatrica, Trapianti di Rene
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Meyer IRCCS - Nefrologia e Dialisi
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino_Regina Margherita - Nefrologia Pediatrica
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Daegu Gwang''yeogsi
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnamdo
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Kaunas
country: Lithuania
facility: Hospital of LT University of Health Sciences Kaunas Clinics
city: Klaipeda
country: Lithuania
facility: Klaipeda Children's Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos Children's Hospital Paediatrics Centre
city: Wilayah Persekutuan
country: Malaysia
facility: Hospital Tunku Azizah
state: Kuala Lumpur
city: Seremban
country: Malaysia
facility: Hospital Tuanku Ja'afar
state: Negeri Sembilan
city: Shah Alam
country: Malaysia
facility: Hospital Selayang
state: Selangor
city: Subang Jaya
country: Malaysia
facility: Sunway Medical Centre
state: Selangor
city: Kelantan
country: Malaysia
facility: Hospital Universiti Sains Malaysia
city: Aguascalientes
country: Mexico
facility: Sitio Alfredo Chew Wong | Aguascalientes, Mexico
state: Agguascalientes
city: Ciudad de Mexico
country: Mexico
facility: Instituto Veracruzano en Investigación Clinica SC
state: Distrito Federal
city: México D.F.
country: Mexico
facility: Hospital Infantil de México "Dr. Federico Gómez"
state: Distrito Federal
city: México, D.F.
country: Mexico
facility: Instituto Nacional de Pediatría
state: Distrito Federal
city: Ixtapaluca
country: Mexico
facility: Hospital Regional de Alta Especialidad Ixtapaluca
state: Estado De Mexico
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Bialystok
country: Poland
facility: Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Warszawa
country: Poland
facility: Dzieciecy Szpital Kliniczny im. Jozefa Brudzinskiego
city: Warszawa
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka"
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny UM we Wroclawiu
city: Missing
country: Portugal
facility: Hospital Santa Maria | Centro de Investigacao Clinica
state: Lisboa
city: Braga
country: Portugal
facility: Centro Clinico Academico Braga | Braga, Portugal
city: Coimbra
country: Portugal
facility: Hospital Pediátrico de Coimbra I ULS Coimbra
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto | Servico de Investigacao Clinica
city: Soweto
country: South Africa
facility: Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit
state: Gauteng
city: Barcelona
country: Spain
facility: Ciutat Sanitaria i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de Sant Joan de Déu
city: Madrid
country: Spain
facility: H Univ. 12 de Octubre | Unidad Pediátrica Inv y EECC (UPIC)
city: Madrid
country: Spain
facility: Hospital la Paz
city: Málaga
country: Spain
facility: University Hospital of Malaga | Unidad de Gestion Clinica de Pediatria
city: Sevilla
country: Spain
facility: Virgen del Rocio University Hospital | Pediatric Nephrology Unit
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus Lund - Barnnefroenheten
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Basel
country: Switzerland
facility: Universitäts-Kinderspital UKBB
state: Basel-Stadt
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
city: Geneva
country: Switzerland
facility: Hopital des Enfants HUG
city: Guishan
country: Taiwan
facility: Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Adana
country: Turkey
facility: Cukurova Univ. Tip. Fak. Balcali Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Baskent Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Health Ministry Of Türkiye Republic Ankara Bilkent City Hospital
city: Istanbul
country: Turkey
facility: Istanbul Faculty of Medicine, Department of Internal Medicine, Department of Pediatrics
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa - Cocuk Nefrolojisi
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty | Pediatric Nephrology
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
Study officials:
References: