MedPath

A Study of Tofacitinib in Patients With Ulcerative Colitis in Stable Remission

Phase 4
Terminated
Conditions
Ulcerative Colitis
Interventions
Drug: CP-690,500 5 mg
Drug: CP-690,550 10 mg
Registration Number
NCT03281304
Lead Sponsor
Pfizer
Brief Summary

This study is a follow up study for subjects with Ulcerative Colitis (UC) in stable remission designed to evaluate flexible dosing of CP-690,550.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
140
Inclusion Criteria
  • Currently enrolled in Study A3921139 receiving CP-690,550 10 mg BID for at least 2 years consecutively.
  • In stable remission on CP-690,550 10 mg BID
  • Agree to use highly effective contraception
  • Negative pregnancy test
  • Comply with visits, treatments, lab tests, diary and other study procedures
  • Signed and dated informed consent document.
Read More
Exclusion Criteria
  • Subjects who were initially assigned to tofacitinib 10 mg BID at baseline of Study A3921139 whose tofacitinib dose was reduced to 5 mg BID due to safety or efficacy.

  • Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis or findings suggestive of Crohn's disease

  • Likely to require surgery for ulcerative colitis during study

  • Expected to receive any prohibited medication

  • Expected to receive live or attenuated virus vaccination during study

  • Women who are pregnant or breastfeeding or planning to become pregnant during the study

  • Evidence of colonic malignancy or any dysplasia

  • Acute or chronic medical or psychiatric condition that may increase risk of participation

  • Investigator site staff member

  • Subjects likely to be uncooperative or unable to comply with study procedures

  • Participation in other studies involving investigational drugs during study

  • Subjects with any of the following risk factors for pulmonary embolism at baseline as defined by EMA's PRAC:

    • has heart failure;
    • has inherited coagulation disorders;
    • has had venous thromboembolism, either deep venous thrombosis or pulmonary embolism;
    • is taking combined hormonal contraceptives or hormone replacement therapy;
    • has malignancy (association is strongest with cancers other than non-melanoma skin cancers);
    • is undergoing major surgery
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CP-690,550 5 mgCP-690,500 5 mgCP-690,550 5 mg tablet by mouth twice a day (BID)
CP-690,550 10 mgCP-690,550 10 mgCP-690,550 10 mg BID
Primary Outcome Measures
NameTimeMethod
Number of Participants With Remission Based on Modified Mayo Score at Month 6Month 6

Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0 at Month 6. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Vital Sign AbnormalitiesBaseline up to 43 months

Vital signs abnormality criteria included: 1) a) diastolic blood pressure (DBP) of (less than) \<50 millimeter of mercury (mmHg), b) change greater than equal to (\>=) 20 mmHg increase, c) change \>=20 mmHg decrease; 2) a) systolic blood pressure (SBP) of \<90 mmHg, b) change \>=30 mmHg increase, c) change \>=30 mmHg decrease; 3) a) pulse rate value of \<40 beats per minute (bpm), b) pulse rate \>120 bpm. Only those categories in which at least 1 participant had data were reported.

Change From Baseline in Modified Mayo Score at Month 6Baseline, Month 6

Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease.

Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42Baseline, Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total modified partial mayo score range from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease.

Number of Participants With Serious InfectionsBaseline up to 43 months

Serious infections were defined as any infections (viral, bacterial, and fungal) requiring parenteral antimicrobial therapy, hospitalization for treatment, or meeting other criteria that require the infection to be classified as serious adverse event. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events.

Number of Participants With Clinical Laboratory AbnormalitiesBaseline up to 27 months

Abnormality criteria: Hematology: hemoglobin(Hg): \<0.8\* lower limit of normal (LLN); hematocrit: \<0.8\*LLN; lymphocytes: \<0.8\* LLN; lymphocytes/leukocytes: \<0.8\*LLN; erythrocytes: \<0.8\*LLN; erythrocytes mean corpuscular volume: \<0.9\*LLN; erythrocytes mean corpuscular Hg: \<0.9\*LLN; reticulocytes, reticulocytes/erythrocytes:\>1.5\* upper limit of normal (ULN); neutrophils, neutrophils/leukocytes: \>1.2\*ULN; basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes/leukocytes: \>1.2\*ULN; leukocyte esterase: \>=1; Clinical chemistry: bicarbonate:\<0.9\*LLN, bilirubin: \>1.5\*ULN; indirect bilirubin: \>1.5\* ULN; aspartate aminotransferase(AT): \>3.0\*ULN; alanine AT: \>3.0\*ULN; gamma glutamyl transferase: \>3.0\* ULN; creatine kinase: \>2.0\*ULN; potassium: \>1.1\*ULN; blood urea nitrogen: \>1.3\*ULN; creatinine: \>1.3\*ULN; urate: \>1.2\*ULN; cholesterol: \>1.3\*ULN; HDL-cholesterol: \<0.8\* LLN; LDL-cholesterol: \>1.2\*ULN; triglycerides: \>1.3\*ULN; glucose: \>1.5\*ULN; and urine Hg \>=1.

Number of Participants With Clinically Significant Laboratory Abnormalities Leading to Study Treatment DiscontinuationBaseline up to 43 months

Laboratory abnormalities leading to study treatment discontinuation: 2 sequential neutrophil counts \<750 neutrophils per cubic millimeter (mm\^3); 2 sequential lymphocyte counts \<500 lymphocytes/mm\^3; 2 sequential hemoglobin \<8.0 grams per deciliter; 2 sequential platelet counts \<75000 platelets/mm\^3; 2 sequential AST or ALT elevations \>=3\*ULN with at least one total bilirubin value \>=2\*ULN; 2 sequential AST or ALT elevations \>=3\*ULN accompanied by signs or symptoms consistent with hepatic injury; 2 sequential AST or ALT elevations \>=5\*ULN; 2 sequential increases in creatinine \>50% and \>0.5 milligrams per deciliter over A3921139 baseline; 2 sequential CK elevations \>10\*ULN unless the causality is known not to be medically serious (eg, exercise induced).

Number of Participants With Clinically Significant Physical Examinations AbnormalitiesBaseline up to 43 months

Physical examination included assessment of the weight, general appearance, eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and lymph nodes. Clinical significance was assessed by the Investigator.

Number of Participants With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42Months 6, 18, 30 and 42

Remission as per total mayo score was defined by a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and physician global assessment (PGA), each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.

Change From Baseline in Total Mayo Score at Month 6Baseline, Month 6

Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.

Change From Baseline in Total Mayo Score at Months 18, 30 and 42Baseline, Months 18, 30 and 42

Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.

Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Level at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Change From baseline in hs-CRP level (in milligrams per liter \[mg/L\]) is reported.

Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier MethodUp to Month 42

Time to loss of remission(flare): time from first drug administration until time of meeting loss of remission criteria based on modified mayo score. Loss of remission: meeting at least (\>=)1 criteria: increase from Baseline in rectal bleeding subscore by \>=1 point and increase in endoscopic subscore by \>=1 point; increase from Baseline in rectal bleeding subscore by \>=2 points and endoscopic subscore \>0; increase in stool frequency subscore by \>=2 points and increase in endoscopic subscore by \>=1 point; increase in endoscopic subscore by \>=2 points. Modified mayo score included 3 components: stool frequency, rectal bleeding and endoscopic subscores: Modified mayo score included 3 components: stool frequency, rectal bleeding and endoscopic subscores, each subscore graded from 0 to 3 with higher scores for each score=more severe disease. All scores summed up to give total modified mayo score range from 0 to 9; higher scores=more severe disease.

Number of Participants With Remission Based on Modified Mayo Score at Months 18, 30 and 42Months 18, 30 and 42

Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease.

Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6Baseline, Months 1, 3 and 6

Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total Modified partial mayo score ranges from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease.

Change From Baseline in Partial Mayo Score at Months 1, 3 and 6Baseline, Months 1, 3 and 6

Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score range from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.

Number of Participants With Mucosal Healing at Months 6, 18, 30 and 42Months 6, 18, 30 and 42

Mucosal healing in participants was defined as the mayo endoscopic subscore of 0 or 1. The Mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher scores indicated more severe disease.

Number of Participants With Clinical Response Based on Mayo Score at Months 6, 18, 30 and 42Months 6, 18, 30 and 42

Clinical response was defined as a decrease from baseline in mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a mayo score range of 0 to 12, where higher scores indicating more severe disease.

Change From Baseline in Fecal Calprotectin at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Change from baseline in fecal calprotectin (in micrograms per gram \[mcg/g\]) was reported.

Number of Participants With Remission Based on Modified Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Remission as per modified partial mayo score was defined as stool frequency subscore of 0 or 1, and rectal bleeding sub score of 0 at the specified time points. Modified partial mayo scores consisted of 2 components: stool frequency and rectal bleeding: each subscore graded from 0 to 3 with higher scores for each score = more severe disease. These scores were summed up to give a total modified partial mayo score range of 0 to 6; where higher scores indicating more severe disease.

Number of Participants With Remission Based on Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Remission as per partial mayo score was defined as partial mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score range from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.

Change From Baseline in Modified Mayo Score at Months 18, 30 and 42Baseline, Months 18, 30 and 42

Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease.

Change From Baseline in Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42Baseline, Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score ranges from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)Baseline up to 43 months

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs included both serious and all non-serious adverse events (irrespective of frequency threshold used to report other AEs in safety section).

Number of Participants With Opportunistic Infections, All Malignancy, Gastrointestinal Perforation and Cardiovascular Events Adjudicated by Adjudication CommitteeBaseline up to 43 months

Number of participants with adjudicated opportunistic infections including herpes zoster (non-adjacent or \>2 adjacent dermatomes); all malignancies including non-melanoma skin cancer; gastrointestinal perforation and cardiovascular events including pulmonary embolism and cerebrovascular accident, adjudicated by adjudication committee were reported.

Trial Locations

Locations (79)

Clinical Applications Laboratories, Inc.

🇺🇸

San Diego, California, United States

Bristol Hospital

🇺🇸

Bristol, Connecticut, United States

Connecticut Clinical Research Institute

🇺🇸

Bristol, Connecticut, United States

Central Connecticut Endoscopy Center

🇺🇸

Plainville, Connecticut, United States

Chevy Chase Endoscopy Center

🇺🇸

Chevy Chase, Maryland, United States

Clinical Research Institute of Michigan, LLC

🇺🇸

Troy, Michigan, United States

Columbia University Medical Center Research Pharmacy/ Milstein Hospital

🇺🇸

New York, New York, United States

NYU Langone Long Island Clinical Research Associates

🇺🇸

Lake Success, New York, United States

Great Lakes Gastroenterology Research, LLC

🇺🇸

Mentor, Ohio, United States

Columbia University Irving Medical Center

🇺🇸

New York, New York, United States

Christus Trinity Mother Frances Endoscopy Center

🇺🇸

Tyler, Texas, United States

Tyler Research Institute, LLC

🇺🇸

Tyler, Texas, United States

Alpine Medical Group

🇺🇸

Salt Lake City, Utah, United States

Wasatch Clinical Research, LLC

🇺🇸

Salt Lake City, Utah, United States

London Health Sciences Centre - University Hospital

🇨🇦

London, Ontario, Canada

UZ Leuven (University Hospital Leuven), Campus Gasthuisberg

🇧🇪

Leuven, Belgium

Royal University Hospital

🇨🇦

Saskatoon, Saskatchewan, Canada

Nemocnice Strakonice a.s.

🇨🇿

Strakonice, Czechia

CHU de Bordeaux Hopital Haut Leveque

🇫🇷

Pessac, France

CHU Hotel Dieu

🇫🇷

Nantes, France

Universitaetsklinikum Schleswig-Holstein

🇩🇪

Kiel, Germany

Szent Janos Korhaz és Eszak-budai Egyesitett Korhazak

🇭🇺

Budapest, Hungary

Pannonia Maganorvosi Centrum Kft.

🇭🇺

Budapest, Hungary

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz Endoszkopos Laboratorium

🇭🇺

Gyula, Hungary

Università "Magna Graecia" di Catanzaro

🇮🇹

Catanzaro, CZ, Italy

Fukuoka University Chikushi Hospital

🇯🇵

Chikushino, Fukuoka, Japan

Aichi Medical University Hospital

🇯🇵

Nagakute, Aichi, Japan

Osaka Medical and Pharmaceutical University Hospital

🇯🇵

Takatsuki-shi, Osaka, Japan

Shiga University of Medical Science Hospital

🇯🇵

Otsu, Shiga, Japan

Showa University Hospital

🇯🇵

Shinagawa-ku, Tokyo, Japan

Hiroshima University Hospital

🇯🇵

Hiroshima, Japan

Toho University Sakura Medical Center

🇯🇵

Chiba, Japan

Keio University Hospital

🇯🇵

Tokyo, Japan

Academic Medical Centre

🇳🇱

Amsterdam, Netherlands

Southern District Health Board

🇳🇿

Dunedin, New Zealand

Endoskopia Sp. z o.o.

🇵🇱

Sopot, Poland

Federal State Budgetary Institution "State Scientific Centre of Coloproctology

🇷🇺

Moscow, Russian Federation

Lexmedica

🇵🇱

Wroclaw, Poland

LLC Novosibirskiy Gastrocenter

🇷🇺

Novosibirsk, Russian Federation

Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology

🇷🇸

Belgrade, Serbia

Military Medical Academy, Clinic for Gastroenterology and Hepatology

🇷🇸

Belgrade, Serbia

Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

Medak s.r.o.

🇸🇰

Bratislava, Slovakia

Gastro I., s.r.o., Gastroenterologicka ambulancia

🇸🇰

Presov, Slovakia

Kingsbury Hospital

🇿🇦

Claremont, Cape Town, South Africa

Chris Hani Baragwanath Academic Hospital

🇿🇦

Soweto, Johannesburg, South Africa

Wits Clinical Research (WCR) Bara Site, Chris Hani Baragwanath Academic Hospital

🇿🇦

Soweto, Johannesburg, Gauteng, South Africa

Endocare Research Centre

🇿🇦

Paarl, Western CAPE, South Africa

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Regional Municipal Non-Profit Enterprise "Chernivtsi Regional Clinical Hospital" Surgery Departm

🇺🇦

Chernivtsi, Ukraine

Kyiv Municipal Clinical Hospital #18

🇺🇦

Kyiv, Ukraine

Vinnytsia Regional Clinical Hospital for War Veterans, Therapeutics Dept. No. 2

🇺🇦

Vinnytsia, Ukraine

MI Uzhgorod Regional Hospital

🇺🇦

Uzhgorod, Ukraine

University Hospitals Bristol NHS Foundation Trust

🇬🇧

Bristol, Avon, United Kingdom

Alabama Medical Group, P.C.

🇺🇸

Mobile, Alabama, United States

Memorial Hermann Hospital

🇺🇸

Houston, Texas, United States

The University of Texas Health Science Center at Houston (UTHealth)- McGovern Medical School

🇺🇸

Houston, Texas, United States

Cotton-O'Neil Clinical Research Center, Digestive Health

🇺🇸

Topeka, Kansas, United States

Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital

🇯🇵

Sapporo, Hokkaido, Japan

MGG Group Co., Inc., Chevy Chase Clinical Research

🇺🇸

Chevy Chase, Maryland, United States

Kyung Hee University Hospital

🇰🇷

Seoul, Korea, Republic of

Kitasato University Kitasato Institute Hospital

🇯🇵

Minato-ku, Tokyo, Japan

Advanced Medical Research Center

🇺🇸

Port Orange, Florida, United States

Florida Medical Clinic, P.A.

🇺🇸

Zephyrhills, Florida, United States

Eastside Endoscopy Center

🇺🇸

Macomb, Michigan, United States

Kurume University Hospital

🇯🇵

Kurume, Fukuoka, Japan

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Clinical Hospital Centre Zvezdara

🇷🇸

Belgrade, Serbia

Tokyo Medical And Dental University Hospital, Faculty of Medicine

🇯🇵

Bunkyo-ku, Tokyo, Japan

Tokai University Hachioji Hospital

🇯🇵

Hachioji, Tokyo, Japan

Osaka Metropolitan University Hospital

🇯🇵

Osaka, Japan

Hanyang University Guri Hospital

🇰🇷

Gyeonggi-do, Korea, Republic of

North Shore Hospital (Waitemata District Health Board)

🇳🇿

Takapuna, Auckland, New Zealand

Christchurch Hospital (Canterbury District Health Board)

🇳🇿

Christchurch, New Zealand

Federal State Budgetary Scientific Institution "Scientific Research Institute of Physiology

🇷🇺

Novosibirsk, Russian Federation

General Hospital "Djordje Joanovic"

🇷🇸

Zrenjanin, Serbia

Panorama Mediclinic

🇿🇦

Panorama, Western CAPE, South Africa

KM Management spol. s.r.o.

🇸🇰

Nitra, Slovakia

Surgicare of Mobile

🇺🇸

Mobile, Alabama, United States

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