Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year
- Conditions
- Crohn Disease
- Interventions
- Biological: Ustekinumab (6 mg/kg)Biological: Adalimumab (40 mg)Biological: Ustekinumab (90 mg)
- Registration Number
- NCT03464136
- Lead Sponsor
- Janssen Scientific Affairs, LLC
- Brief Summary
The purpose of this study is to compare the efficacy of treatment with ustekinumab or adalimumab in biologic naive participants with moderately-to-severely active Crohn's disease (CD) who have previously failed or were intolerant to conventional therapy (corticosteroids and/or immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate), as measured by clinical remission at one year.
- Detailed Description
This study compares the safety and efficacy of ustekinumab versus adalimumab. It will consist of screening (within 1- 5 weeks prior to Week 0), treatment phase (Weeks 0 to 52), and follow-up phase (up to Week 76). The primary hypothesis is that ustekinumab is superior to adalimumab as measured by clinical remission after one year of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy; CD-related healthcare utilization; patient-reported outcomes (PROs); laboratory evaluations; biomarkers; review of concomitant medications and adverse events (AEs); and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants will randomly be assigned to receive either ustekinumab or adalimumab. No participants will be treated with placebo only.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 386
- Has Crohn's Disease (CD) or fistulizing CD of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, and/or endoscopy
- Has moderately-to-severely active CD with a baseline Crohn's disease activity index (CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450
- Has one or more ulceration on screening ileocolonoscopy (which by definition, would result in an Simple Endoscopic Score for Crohn's Disease [SES-CD] of at least 3)
- Has failed or was intolerant to conventional therapy (corticosteroids, azathioprine [AZA], 6-mercaptopurine [6-MP] and/or methotrexate [MTX]) at adequate doses or is corticosteroid dependent
- Has not previously received an approved biologic for Crohn's Disease (i.e., infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or approved biosimilars of these agents)
- Participants on oral corticosteroids (e.g., prednisone, budesonide) at a prednisone-equivalent dose of <=40 or milligram/day (mg/day) or <=9 mg/day of budesonide are budesonide <=9 mg/day are permitted if doses are stable for 3 weeks prior to baseline
- Participants on AZA, 6-MP, or MTX at screening (or recently prior), must discontinue these medications at least 3 weeks prior to baseline
- Has complications of CD that are likely to require surgery or would confound the ability to assess the effect of ustekinumab or adalimumab treatment using the CDAI, such as: active stoma; short-gut syndrome and severe or symptomatic strictures or stenosis
- Currently has, or is suspected to have, an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior for intra-abdominal abscesses, if there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present
- Has had any kind of bowel resection within 6 months prior to baseline or other intra-abdominal surgery or a hospital admission for bowel obstruction within 3 months prior to baseline
- Has a stool culture or other examination positive for an enteric pathogen, including Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen
- Has received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 2 weeks of baseline
- Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or infected skin wounds or ulcers
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2 (Adalimumab) Placebo for Adalimumab Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w. Group 1 (Ustekinumab) Ustekinumab (6 mg/kg) Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals. Group 2 (Adalimumab) Adalimumab (40 mg) Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w. Group 1 (Ustekinumab) Ustekinumab (90 mg) Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals. Group 1 (Ustekinumab) Placebo for Ustekinumab Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinical Remission at Week 52 Week 52 Percentage of participants with clinical remission at Week 52 were assessed. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than (\<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
- Secondary Outcome Measures
Name Time Method Percentage of Participants in Patient Reported Outcome (PRO)-2 Symptom Remission at Week 52 Week 52 PRO2 evaluated 2 patient-reported symptoms: the frequency of liquid or soft stools (total number of soft/liquid stools in the last 7 days) and abdominal pain (on a 4-point scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe). A weekly score was calculated for the liquid or soft stool frequency and a separate weekly score was calculated for abdominal pain, in each case based on daily symptom reporting. PRO-2 symptom remission was defined as an abdominal pain (AP) mean daily score at or below 1 and also stool frequency (SF) mean daily score at or below 3, that is, AP \<=1 and SF \<=3. PRO2 is a composite index consisting of weighted scoring of both variables. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease.
Percentage of Participants With Clinical Response Through Week 52 Weeks 2, 8, 16, 24, 32, 40, 48, and 52 Percentage of participants with clinical response at each postbaseline visit through Week 52 were reported. Clinical response through Week 52 was defined as a reduction from baseline in the CDAI score of \>=100 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Clinical Remission Through Week 52 Weeks 2, 8, 16, 24, 32, 40, 48, and 52 Percentage of participants with clinical remission at each postbaseline visit through Week 52 were reported. Clinical remission was defined as a CDAI score of \<150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Serious Adverse Events (SAEs) Up to Week 52 and up to Week 76 Percentage of participants with SAEs were reported. A SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Coronavirus disease 2019 (COVID-19) related adverse events are adverse events with any of the following preferred terms "COVID-19", "Asymptomatic COVID-19", "Suspected COVID-19", "COVID-19 pneumonia", "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positive" or with a reported term containing the string "COVI.
Percentage of Participants With Clinical Response at Week 52 Week 52 Percentage of participants with clinical response at Week 52 were assessed. Clinical response at Week 52 was defined as a reduction from baseline in the CDAI score of greater than or equal (\>=) 100 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Adverse Events (AEs) Up to Week 52 and up to Week 76 Percentage of participants with AE were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Percentage of Participants With Corticosteroid-free Remission at Week 52 Week 52 Percentage of participants with Corticosteroid-free remission at Week 52 were assessed. Corticosteroid-free remission was defined as CDAI score \<150 points at Week 52 and not taking any corticosteroids for at least 30 days prior to Week 52. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Endoscopic Remission at Week 52 Week 52 Percentage of participants with endoscopic remission at Week 52 were assessed. Endoscopic remission was defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) score less than or equal to (\<=) 3, or SES-CD =0 for participants who entered the study with a SES-CD =3 at Week 52. The SES-CD evaluates 4 endoscopic variables (ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis) each rated from 0 (best) to 3 (worst) in 5 segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable is the sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.
Percentage of Participants With Durable Clinical Remission at Week 52 Week 52 Percentage of participants with durable clinical remission at Week 52 were reported. Clinical remission was defined as CDAI score \<150 at Week 52 and was \>= 80% of all visits between Week 16 and Week 52. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Weeks 2, 8, 16, 24, 32, 40, 48, and 52 Percentage of participants with AP improvement through Week 52 were reported. AP improvement was defined as at least 1 point or greater improvement in mean daily CDAI AP score (ranges from 0 to 3 where higher score indicates severity of pain) from baseline, or a mean score of zero among participants with mean AP\>0 at baseline, compared at each visit through Week 52.
Percentage of Participants With Clinical and Biomarker Remission at Weeks 8, 16 and 52 At Weeks 8, 16 and 52 Percentage of participants with clinical and biomarker remission was defined as the percentage of participants with CDAI \<150, CRP \<= 3 mg/L, and also fecal calprotectin \<=250 micrograms per gram (mcg/g). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Infections Up to Week 52 and up to Week 76 Percentage of participants with infections were reported.
Percentage of Participants With Anti-drug Antibodies Up to Week 52 Percentage of participants with anti-drug antibodies were reported. Serum samples were assessed for anti-drug antibodies. Anti-drug assays were performed for ustekinumab and adalimumab.
Percentage of Participants With Clinical Remission at Week 16 Week 16 Percentage of participants with clinical remission (defined as CDAI \<150 points) at Week 16 were assessed. Clinical remission was defined as a CDAI score of \< 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Durable Clinical Response at Week 52 Week 52 Percentage of participants with durable clinical response at Week 52 were reported. Durable clinical response was defined as CDAI score decreased at least 100 from baseline or CDAI \<150 at Week 52 and was \>= 80% of all visits between Week 16 and Week 52. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Weeks 2, 8, 16, 24, 32, 40, 48, and 52 Number of participants with reduction in frequency of diarrhea were reported. Reduction in frequency of diarrhea was defined as a reduction of at least 3 (or a mean number \<1) in SF (that is, mean daily number of liquid or very soft stools from CDAI score \[ranges from 0 to 3 where higher score indicates severity of pain\] in the week prior to the visit) from baseline, among subjects with mean SF \>1 at baseline, compared at each visit through Week 52.
Percentage of Participants With Serious Infections Up to Week 52 and up to Week 76 Percentage of participants with serious infections were reported.
Trial Locations
- Locations (180)
2-nd MHAT
🇧🇬Sofia, Bulgaria
CISSS de la Monteregie Centre
🇨🇦Greenfield Park, Quebec, Canada
CMIIM, Centre médical L'Enjeu
🇨🇦Mont-Royal, Quebec, Canada
Fakultní nemocnice u sv. Anny v Brn
🇨🇿Brno, Czechia
Diagnostic Consulting Center Mladost - M Varna
🇧🇬Varna, Bulgaria
University of Calgary
🇨🇦Calgary, Alberta, Canada
McMaster University
🇨🇦Hamilton, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Nemocnice Horovice, a.s.
🇨🇿Horovice, Czechia
CHU Amiens
🇫🇷Amiens, France
CHU Saint Etienne
🇫🇷Saint Priest en jarez, France
Hepato-gastroenterologie HK, s.r.o.
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
ISCARE a.s.
🇨🇿Praha 9, Czechia
CHRU Montpellier - Hopital Saint-Eloi
🇫🇷Montpellier, France
Hotel Dieu
🇫🇷Nantes, France
Alabama Medical Group
🇺🇸Mobile, Alabama, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
Precision Research Institute
🇺🇸San Diego, California, United States
Gastro Associates of Fairfield County PC
🇺🇸Bridgeport, Connecticut, United States
Western Connecticut Health Network/Danbury Hospital
🇺🇸Danbury, Connecticut, United States
Gastro Florida
🇺🇸Clearwater, Florida, United States
Florida Research Network, LLC
🇺🇸Gainesville, Florida, United States
Gastroenterology Group Of Naples
🇺🇸Naples, Florida, United States
Advanced Medical Research Center
🇺🇸Port Orange, Florida, United States
Medstar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Grand Teton Research Group, PLLC
🇺🇸Idaho Falls, Idaho, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Chesterfield, Michigan, United States
Center for Advanced Gastroenterology
🇺🇸Maitland, Florida, United States
Florida Center For Gastroenterology
🇺🇸Largo, Florida, United States
Apex Clinical Research
🇺🇸Tampa, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Atlanta Gastroenterology Specialists, PC
🇺🇸Suwanee, Georgia, United States
Health Science Research Center
🇺🇸Pratt, Kansas, United States
Tri-State Gastroenterology Assoc
🇺🇸Crestview Hills, Kentucky, United States
Huron Gastroenterology Associates Center for Digestive Care
🇺🇸Ypsilanti, Michigan, United States
Gastroenterology Associates Of Hazard
🇺🇸Hazard, Kentucky, United States
Mercy Clinic East Community
🇺🇸Saint Louis, Missouri, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Dayton Gastroenterology, Inc
🇺🇸Dayton, Ohio, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Gastroenterology Research of America, LLC
🇺🇸San Antonio, Texas, United States
Tyler Research Institute, LLC
🇺🇸Tyler, Texas, United States
Gastroenterology Associates of Tidewater
🇺🇸Chesapeake, Virginia, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
CroNOLA, LLC
🇺🇸Houma, Louisiana, United States
Texas Digestive Disease Consultants
🇺🇸Southlake, Texas, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Louisiana Research Center, LLC
🇺🇸Shreveport, Louisiana, United States
Chevy Chase Clinical Research
🇺🇸Chevy Chase, Maryland, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
NYU Langone Long Island Clinical Research Associates
🇺🇸Great Neck, New York, United States
Premier Medical Group Of The Hudson Valley, Pc
🇺🇸Poughkeepsie, New York, United States
Digestive Health Partners
🇺🇸Asheville, North Carolina, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Ohio State University Hospital
🇺🇸Columbus, Ohio, United States
Saratoga Schenectady Gastroenterology Associates
🇺🇸Burnt Hills, New York, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Duke University Hospital Medical Center
🇺🇸Raleigh, North Carolina, United States
Wilmington Gastroenterology Associates
🇺🇸Wilmington, North Carolina, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Gastroenterology Associates P.A.
🇺🇸Greenville, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Great Lakes Gastroenterology Research, LLC
🇺🇸Mentor, Ohio, United States
Fargo Gastroenterology Clinic, PC
🇺🇸Fargo, North Dakota, United States
Northshore Gastroenterology Research, LLC
🇺🇸Beachwood, Ohio, United States
TriHealth Digestive Institute
🇺🇸Cincinnati, Ohio, United States
Allegheny-Singer Research Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Digestive Disease Specialists Inc
🇺🇸Oklahoma City, Oklahoma, United States
DHAT Research Institute
🇺🇸Garland, Texas, United States
Gastroenterology Associates of Central Virginia
🇺🇸Lynchburg, Virginia, United States
University of Texas at Houston Medical School
🇺🇸Houston, Texas, United States
McGuire VAMC
🇺🇸Richmond, Virginia, United States
Aztec Clinical Research, Inc.
🇺🇸Channelview, Texas, United States
Verity Research, Inc
🇺🇸Fairfax, Virginia, United States
Digestive And Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Virginia Gastroenterology Institute
🇺🇸Suffolk, Virginia, United States
MHAT Rousse
🇧🇬Rousse, Bulgaria
Mater Hospital Brisbane Inflammatory Bowel Diseases
🇦🇺South Brisbane, Australia
Washington Gastroenterology, PLLC
🇺🇸Tacoma, Washington, United States
Monash Health, Monash Medical Centre
🇦🇺Clayton, Australia
Alfred Hospital
🇦🇺Melbourne, Australia
UZ Gent
🇧🇪Gent, Belgium
St John of God Subiaco Hospital
🇦🇺Subiaco, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, Australia
UZ Leuven
🇧🇪Leuven, Belgium
Hospital Das Clinicas Da Ufmg
🇧🇷Belo Horizonte - MG, Brazil
CHwapi
🇧🇪Tournai, Belgium
Inst Goiano Gastroenterologia e Endoscopia Digest Ltda - Clinica de Gastro
🇧🇷Goiania, Brazil
Endogastro Clínica de Gastroenterologia e Endoscopia Digestiva Lida
🇧🇷Juiz de Fora, Brazil
Hospital das Clinicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
🇧🇷Ribeirao Preto, Brazil
UMHAT 'Dr. Georgi Stranski', EAD
🇧🇬Pleven, Bulgaria
Universidade Federal do Rio de Janeiro - Faculdade de Medicina
🇧🇷Rio de Janeiro, Brazil
Hospital Copa D'Or
🇧🇷Rio de Janeiro, Brazil
Fundacao do ABC Centro Universitario FMABC
🇧🇷Santo Andre, Brazil
Hopital Saint Louis
🇫🇷Paris, France
Clinique Ambroise Pare
🇫🇷Toulouse, France
Uniklinikum Heidelberg
🇩🇪Heidelberg, Germany
Réthy Pál Kórház - Rendelőintézet
🇭🇺Békéscsaba, Hungary
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
AOU Policlinico G.Martino
🇮🇹Messina, Italy
Asklepios Westklinikum
🇩🇪Hamburg, Germany
MVZ Portal10
🇩🇪Muenster, Germany
Magyar Honvedseg Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
🇭🇺Miskolc, Hungary
Markusovszky Egyetemi Oktatokorhaz
🇭🇺Szombathely, Hungary
Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
ASST Fatebenefratelli Sacco
🇮🇹Milano, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Ospedale Villa Sofia-Cervello
🇮🇹Palermo, Italy
Azienda Ospedaliera G.Salvini Ospedale di Rho
🇮🇹RHO, Italy
Azienda Ospedaliera Universitaria 'Policlinico Tor Vergata'
🇮🇹Roma, Italy
Azienda Complesso Ospedaliero San Filippo Neri
🇮🇹Roma, Italy
Fondazione Policlinico Gemelli Università Cattolica
🇮🇹Roma, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
AO Ordine Mauriziano
🇮🇹Torino, Italy
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
The Catholic university of Korea, St. Vincent's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
VUMC Amsterdam
🇳🇱Amsterdam, Netherlands
Rijnstate Ziekenhuis
🇳🇱Arnhem, Netherlands
UMCG
🇳🇱Groningen, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Sint Franciscus Gasthuis
🇳🇱Rotterdam, Netherlands
Ikazia Ziekenhuis
🇳🇱Rotterdam, Netherlands
Gastromed Kralisz Romatowski Stachurska Sp. j.
🇵🇱Bialystok, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Krakow, Poland
Synexus Polska Sp z o o
🇵🇱Gdansk, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddzial Gastroenterologii
🇵🇱Lublin, Poland
Centrum Medyczne Plejady
🇵🇱Krakow, Poland
Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
🇵🇱Lodz, Poland
Centrum Medyczne Medyk
🇵🇱Rzeszow, Poland
Melita Medical Sp. z o.o.
🇵🇱Wroclaw, Poland
Rostov State Medical University
🇷🇺Rostov-On-Don, Russian Federation
Endoskopia Sp z o o z siedziba w Sopocie
🇵🇱Sopot, Poland
Centralny Szpital Kliniczny MSWiA w Warszawie
🇵🇱Warsaw, Poland
Gabinety Lekarskie Bodyclinic
🇵🇱Warszawa, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Vivamed Jadwiga Miecz
🇵🇱Warszawa, Poland
ETG Zamosc
🇵🇱Zamosc, Poland
OOO MO New Hospital
🇷🇺Ekaterinburg, Russian Federation
Irkutsk State Medical Academy of Postgraduate Education
🇷🇺Irkutsk, Russian Federation
Clinical Hospital Center Zemun
🇷🇸Belgrade, Serbia
GU Moscow Regional Research Clinical Institute n.a. M.F.Vla
🇷🇺Moscva, Russian Federation
Elizavetinskaya hospital
🇷🇺Saint Petersburg, Russian Federation
City Clinical Hospital #31
🇷🇺Saint Petersburg, Russian Federation
GBUZ Respublican Clinical Hospital n.a. GG Kuvatova
🇷🇺Ufa, Russian Federation
City Clinical Hospital # 21
🇷🇺Ufa, Russian Federation
Clinical Hospital Center Zvezdara
🇷🇸Belgrade, Serbia
University Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Clinical Center of Vojvodina
🇷🇸Vojvodina, Serbia
University Clinical Center NIS
🇷🇸Nis, Serbia
Clinical Hospital Center Bezanijska Kosa
🇷🇸Zemun, Serbia
Hosp. Del Mar
🇪🇸Barcelona, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Hosp. de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hosp. Univ. Dr. Josep Trueta
🇪🇸Girona, Spain
Hosp. Univ. Central de Asturias
🇪🇸Oviedo, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Hosp. Virgen Macarena
🇪🇸Sevilla, Spain
Hosp. Univ. Miguel Servet
🇪🇸Zaragoza, Spain
Royal United Hospital
🇬🇧Bath, United Kingdom
Hosp. Univ. Rio Hortega
🇪🇸Valladolid, Spain
Pennine Acute Hospitals-Fairfield General Hospital
🇬🇧Bury, United Kingdom
Kingston Hospital
🇬🇧Kingston upon Thames, United Kingdom
Guy's and St Thomas' Hospital
🇬🇧London, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
Southampton University Hospitals NHS Trust
🇬🇧Southampton, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom