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Clinical Trial NCT06221969 for Type 2 Diabetes is active, not recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
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Novo Nordisk A/SA Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Tirzepatide in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor Phase 3 1,000
Clinical Trial NCT06221969 is designed to study Treatment for Type 2 Diabetes. It is a Phase 3 interventional study that is active, not recruiting, having started on January 16, 2024, with plans to enroll 1,000 participants. Led by Novo Nordisk A/S, it is expected to complete by April 3, 2026. The latest data from ClinicalTrials.gov was last updated on January 27, 2026.
Brief Summary
This study will look at how well CagriSema helps people with type 2 diabetes lower their blood sugar and body weight. CagriSema is a new investigational medicine. Doctors may not yet prescribe CagriSema. CagriSema will be compared to a medicine called tirzepatide that doctors may prescribe in some countries. Participants will get either CagriSema or tirzepatide. Which treatment participant get is decided by chance li...Show More
Official Title
Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) 2.4 mg/2.4 mg s.c. Once Weekly Versus Tirzepatide 15 mg s.c. Once Weekly in Participants With Type 2 Diabetes Inadequately Controlled on Metformin With or Without an SGLT2 Inhibitor
Conditions
Type 2 DiabetesOther Study IDs
- NN9388-4894
- U1111-1282-5561 (Other Identifier) (World Health Organization (WHO))
- 2023-503789-21-00 (Other Identifier) (European Medical Agency (EMA))
NCT ID Number
Start Date (Actual)
2024-01-16
Last Update Posted
2026-01-27
Completion Date (Estimated)
2026-04-03
Enrollment (Estimated)
1,000
Study Type
Interventional
PHASE
Phase 3
Status
Active, not recruiting
Primary Purpose
Treatment
Design Allocation
Randomized
Interventional Model
Parallel
Masking
None (Open Label)
Arms / Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalCagriSema Participants will receive cagrilintide dose 1 and semaglutide dose 2 subcutaneously once-weekly (dose escalation period of 16 weeks) for up to 68 weeks. | Cagrilintide Cagrilintide will be administered subcutaneously. Semaglutide Semaglutide will be administered subcutaneously. |
Active ComparatorTirzepatide Participants will receive tirzepatide dose 1 subcutaneously once-weekly (dose escalation period of 20 weeks) for up to 68 weeks. | Tirzepatide Tirzepatide will be administered subcutaneously. |
Primary Outcome Measures
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Change in glycated haemoglobin (HbA1c) | Measured in percentage (%)-points. | From baseline (week 0) to end of treatment (week 68) |
Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 68) |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Change in HbA1c | Measured in %-points. | From baseline (week 0) to end of treatment (week 68) |
Change in fasting plasma glucose (FPG) | Measured in millimoles per liter (mmol/L). | From baseline (week 0) to end of treatment (week 68) |
Achievement of HbA1c target values of less than (<) 7.0% (<53 millimole per mole [mmol/mol]) | Count of participant | At end of treatment (week 68) |
Achievement of HbA1c target values of less than or equal to (≤) 6.5% (≤ 48 mmol/mol) | Count of participant | From baseline (week 0) to end of treatment (week 68) |
Achievement of greater than or equal to (≥) 5% weight reduction | Count of participant | From baseline (week 0) to end of treatment (week 68) |
Achievement of ≥ 10% weight reduction | Count of participant | From baseline (week 0) to end of treatment (week 68) |
Achievement of ≥ 15 % weight reduction | Count of participant | From baseline (week 0) to end of treatment (week 68) |
Achievement of ≥ 20 % weight reduction | Count of participant | From baseline (week 0) to end of treatment (week 68) |
Change in systolic blood pressure | Measured in millimeters of mercury(mmHg). | From baseline (week 0) to end of treatment (week 68) |
Change in diastolic blood pressure | Measured in mmHg. | From baseline (week 0) to end of treatment (week 68) |
Change in waist circumference | Measured in centimeter (cm). | From baseline (week 0) to end of treatment (week 68) |
Ratio to baseline in lipids: Total cholesterol | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) |
Ratio to baseline in lipids: High-density lipoprotein (HDL) cholesterol | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) |
Ratio to baseline in lipids: Low-density lipoprotein (LDL) cholesterol | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) |
Ratio to baseline in lipids: Very low-density lipoprotein (VLDL) cholesterol | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) |
Ratio to baseline in lipids: Triglycerides | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) |
Ratio to baseline in lipids: non-HDL cholesterol | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) |
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey | The SF-36 v2 will be used to measure differences in quality of life and mental wellbeing. The scores 0-100 (where higher scores indicated a better quality of life and mental wellbeing) from the SF-36 will be converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 United States general population. Measured as score on a scale. | From baseline (week 0) to end of treatment (week 68) |
Change in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) version 3 | IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0-100), Physical Function composite (0-100). Total score (0-100). Higher scores indicate better level of functioning. | From baseline (week 0) to end of treatment (week 68) |
Number of Treatment-emergent Adverse Events (TEAEs) | Count of events | From baseline (week 0) to end of study (week 74) |
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (<54 milligram per deciliter [mg/dL]), confirmed by blood glucose meter) | Count of episodes | From baseline (week 0) to end of study (week 74) |
Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold | Count of episodes | From baseline (week 0) to end of study (week 74) |
Participation Assistant
Eligibility Criteria
Eligible Ages
Adult, Older Adult
Minimum Age
18 Years
Eligible Sexes
All
- Male or female (sex at birth).
- Age 18 years or above at the time of signing the informed consent.
- Diagnosed with type 2 diabetes ≥ 180 days before screening.
- Stable daily dose(s) ≥ 90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator: metformin with or without an sodium-glucose co-transporter-2 (SGLT2) inhibitor.
- HbA1c 7.0-10.5% (53-91 mmol/mol) (both inclusive) as determined by central laboratory at screening.
- Body mass index (BMI) of ≥ 30.0 kilogram per square meter (kg/m^2) at screening. BMI will be calculated in the electronic case report form (eCRF) based on height and body weight at screening.
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
- Renal impairment with estimated Glomerular Filtration Rate < 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) as determined by central laboratory at screening.
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed.
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
Novo Nordisk A/S131 active studies to exploreNo contact data.
195 Study Locations in 8 Countries
Alabama
Synexus Clin Res-Birmingham, Birmingham, Alabama, 35211, United States
Univ of Alabama_Birmingham, Birmingham, Alabama, 35233, United States
Arizona
Prime Medical Group, LLC, Gilbert, Arizona, 85296, United States
Velocity Clinical Research-Phoenix, Phoenix, Arizona, 85006, United States
Synexus Rsch /Cnt Phnx Med C, Phoenix, Arizona, 85020, United States
Arkansas
Arkansas Clinical Research, Little Rock, Arkansas, 72205, United States
Unity Health-Searcy Medical Center, Searcy, Arkansas, 72143, United States
California
Velocity Clin Res-Chula Vista, Chula Vista, California, 91911, United States
Headlands Research California, LLC, Escondido, California, 92025, United States
Neighborhood Healthcare, Escondido, California, 92025, United States
St. Jude Heritage Yorba Linda - Pediatric Ste D, Fullerton, California, 92835, United States
Diabetes & Endocrine Specialists - La Mesa, La Mesa, California, 91942, United States
Diabetes and Endocrine Specialists - La Mesa, La Mesa, California, 91942, United States
Velocity Clin Res San Diego, La Mesa, California, 91942, United States
Clinical Trials Research, Lincoln, California, 95648, United States
Loma Linda Univ Hlth Cr Endo, Loma Linda, California, 92354, United States
Valley Clinical Trials, Inc., Northridge, California, 91325, United States
Desert Oasis Healthcare, Palm Springs, California, 92262, United States
Velocity Clin Res - Panorama, Panorama City, California, 91402, United States
Western University of Health Sciences, Pomona, California, 91766, United States
Endocrinology Josel Cabaccan, San Jose, California, 95148, United States
Mills-Peninsula Medical Center, San Mateo, California, 94401, United States
NorCal Endocrinology and Internal Medicine, San Ramon, California, 94583, United States
Premier Medical Center, Inc., Toluca Lake, California, 91602, United States
Velocity Clin Res - Panorama, Van Nuys, California, 91405, United States
Diablo Clinical Research, Inc., Walnut Creek, California, 94598, United States
Colorado
University of Colorado Hospital, Aurora, Colorado, 80045, United States
Optumcare Clinical Trials,LLC-Golden, Colorado Springs, Colorado, 80906, United States
Florida
Northeast Res Inst. Inc., Jacksonville, Florida, 32204, United States
Clinical Trial Services Corp, Miami, Florida, 33144, United States
Bioclinical Research Alliance, Miami, Florida, 33155, United States
New Horizon Research Center, Miami, Florida, 33165, United States
South Broward Research LLC, Miramar, Florida, 33027, United States
West Orange Endocrinology, Ocoee, Florida, 34761, United States
Optimal Research Sites, Orange City, Florida, 32763, United States
Trans Res Inst for Met & Diab, Orlando, Florida, 32804, United States
Oviedo Medical Research, LLC, Oviedo, Florida, 32765, United States
Georgia
Hope Clin Res & Wellness, Conyers, Georgia, 30094, United States
Center for Adv Res & Education, Gainesville, Georgia, 30501, United States
Urban Family Practice Assoc, Marietta, Georgia, 30067, United States
Endocrine Research Solutions, Roswell, Georgia, 30076, United States
Hawaii
Pacific Diabetes & Endo Ctr, Honolulu, Hawaii, 96813, United States
Idaho
St. Luke's Health System, Boise, Idaho, 83702, United States
Solaris Clinical Research, Meridian, Idaho, 83646, United States
Illinois
Cedar-Crosse Research Center, Chicago, Illinois, 60607, United States
Clinical Invest Special_Gurnee, Gurnee, Illinois, 60031, United States
Endeavor Health, Skokie, Illinois, 60077, United States
Evanston Premier Hlthcr Res, Skokie, Illinois, 60077, United States
Indiana
American Health Network of Indiana, LLC_Greenfield, Greenfield, Indiana, 46140, United States
Iowa
Iowa Diabetes & Endo Res Ctr, West Des Moines, Iowa, 50266, United States
Kansas
Cotton-O'Neil Diab & Endo Ctr, Topeka, Kansas, 66606, United States
Louisiana
Velocity Clin Res Lafayette, Lafayette, Louisiana, 70508, United States
Maryland
MedStar Hlth Res Institute, Hyattsville, Maryland, 20782, United States
Massachusetts
Joslin Diabetes Center, Boston, Massachusetts, 02215, United States
Minnesota
International Diabetes Center, Minneapolis, Minnesota, 55416, United States
Mississippi
Belzoni Clinical Research, Belzoni, Mississippi, 39038, United States
Velocity Clin Res Gulfport, Gulfport, Mississippi, 39503, United States
Missouri
Diabetes & Endo Specialists Inc, Chesterfield, Missouri, 63017, United States
StudyMetrix Research LLC, City of Saint Peters, Missouri, 63303, United States
Amicis Centers of Clinical Research, St Louis, Missouri, 63128, United States
New Mexico
Velocity Clin Res Albuquerque, Albuquerque, New Mexico, 87107, United States
New York
AMC Community Endocrinology, Albany, New York, 12203, United States
Velocity Clin Res Syracuse, East Syracuse, New York, 13057, United States
Southgate Medical Group, LLP, West Seneca, New York, 14224, United States
North Carolina
UNC Eastowne Clinical Research Unit, Chapel Hill, North Carolina, 27514, United States
PharmQuest Life Sciences LLC, Greensboro, North Carolina, 27408, United States
Carteret Medical Group, Morehead City, North Carolina, 28557, United States
Lucas Research Inc., Morehead City, North Carolina, 28557, United States
Piedmont Healthcare/Research, Statesville, North Carolina, 28625, United States
Accellacare, Wilmington, North Carolina, 28401, United States
North Dakota
Plains Clinical Research Center, LLC, Fargo, North Dakota, 58104, United States
Ohio
Remington Davis Inc, Columbus, Ohio, 43215, United States
Advanced Medical Research, Maumee, Ohio, 43537, United States
New Venture Medical Research, Wadsworth, Ohio, 44281-9236, United States
Oklahoma
Lynn Institute of Norman, Norman, Oklahoma, 73072, United States
Pennsylvania
CCT Research, Horsham, Pennsylvania, 19044, United States
Thomas Jefferson University_Philadelphia, Philadelphia, Pennsylvania, 19114, United States
Rhode Island
Clinical Res Collaborative, Cumberland, Rhode Island, 02864, United States
Velocity Clin Res Providence, East Greenwich, Rhode Island, 02818, United States
South Carolina
Velocity Clinical Res-Anderson, Anderson, South Carolina, 29621, United States
Trial Management Associates, Myrtle Beach, South Carolina, 29572, United States
Hillcrest Clinical Research, Simpsonville, South Carolina, 29681-1538, United States
Spartanburg Medical Research, Spartanburg, South Carolina, 29303, United States
Tennessee
AM Diabetes And Endocrinology Center, Bartlett, Tennessee, 38133, United States
Holston Medical Group Pc, Bristol, Tennessee, 37620-7352, United States
Univ Diab & Endo Consultants, Chattanooga, Tennessee, 37411, United States
Jackson Clinic, Jackson, Tennessee, 38305, United States
Holston Medical Group, Kingsport, Tennessee, 37660, United States
Clinical Neuroscience Solutions, Memphis, Tennessee, 38119, United States
HealthStar Physicians PC, Morristown, Tennessee, 37813, United States
Clinical Research Associates, Nashville, Tennessee, 37203, United States
Texas
Arlington Family Res. Ctr Inc, Arlington, Texas, 76012-4637, United States
Velocity Clin Res, Austin, Texas, 78759, United States
UT Health University of Texas, Bellaire, Texas, 77401, United States
Velocity Clin Res, Dallas, Dallas, Texas, 75230, United States
North Texas Endocrine Center, Dallas, Texas, 75231, United States
Synexus Clin Res Dallas, Dallas, Texas, 75234, United States
Cedar Health Research, Dallas, Texas, 75251, United States
PrimeCare Medical Group, Houston, Texas, 77024, United States
JCCT- Juno NW Houston, Houston, Texas, 77040, United States
Discovery MM Services, Inc, Houston, Texas, 77061, United States
PlanIt Research, PLLC, Houston, Texas, 77079, United States
Amir Ali Hassan, MD, PA, Houston, Texas, 77089, United States
Fmc Science, Llc, Lampasas, Texas, 76550, United States
Quality Clinical Research, Inc., San Antonio, Texas, 78209, United States
University of Texas San Antonio, San Antonio, Texas, 78229, United States
NE Clin Res of San Antonio, San Antonio, Texas, 78233, United States
University of Texas San Antonio, San Antonio, Texas, 78284, United States
Consano Clinical Research, LLC, Shavano Park, Texas, 78231, United States
Mt Olympus Medical Research, LLC, Sugar Land, Texas, 77478, United States
DM Clin Rsrch/Fam Diag Clinic, Tomball, Texas, 77375, United States
Utah
Foothill Family Clinic South, Salt Lake City, Utah, 84121, United States
J.Lewis Research Inc, South Jordan, Utah, 84095, United States
Velocity Clin Res-Salt Lk City, West Jordan, Utah, 84088, United States
Virginia
TPMG Clinical Research, Newport News, Virginia, 23606, United States
Washington
Rainier Clin Res Ctr Inc, Renton, Washington, 98057, United States
Wisconsin
Prevea Health, Green Bay, Wisconsin, 54303, United States
Alberta
Centricity Research Calgary Endocrinology, Calgary, Alberta, T2H 2G4, Canada
British Columbia
Guilford Med Clinic, Surrey, British Columbia, V3R 4H6, Canada
TLC Diabetes and Endocrinology, Surrey, British Columbia, V3T 2V6, Canada
Ocean West Research Clinic, Surrey, British Columbia, V3Z 2N6, Canada
Hilltop Medical Clinic, Surrey, British Columbia, V4A 0C1, Canada
New Brunswick
G.A. Research Associates Ltd., Moncton, New Brunswick, E1G 1A7, Canada
Ontario
Centricity Research Brampton Endocrinology, Brampton, Ontario, L6S 0C6, Canada
Milestone Research, London, Ontario, N5W 6A2, Canada
Western Univ. Cnt for Studies in Fam Med, London, Ontario, N6G 2M1, Canada
London Road Diagnostic Clinic and Medical Centre, Sarnia, Ontario, N7T 4X3, Canada
Centricity Research Toronto, Toronto, Ontario, M4G 3E8, Canada
Diabetes Heart Research Centre, Toronto, Ontario, M6G 1M2, Canada
Quebec
Centre Medical Acadie, Montreal, Quebec, H4N 2W2, Canada
ALPHA Recherche Clinique, Québec, Quebec, G3K 2P8, Canada
Ctr de Med Metab de Lanaudiere, Terrebonne, Quebec, J6X 4P7, Canada
Diex Recherche Victoriaville, Victoriaville, Quebec, G6P 3Z8, Canada
West Oshawa
Centricity Research Oshawa, Barrie, West Oshawa, L4N 7L3, Canada
Clin des Mal Lipid de Quebec, Québec, G1V 4W2, Canada
Centre de Recherche Saint-Louis, Québec, G1W 4R4, Canada
Buenos Aires
Buenos Aires Mácula, Ciudad Autonoma de Buenos Aires, Buenos Aires, C1061AAE, Argentina
CICEMO- Consultorio de Investigación Clínica EMO, Ciudad Autonoma de Buenos Aires, Buenos Aires, C1405BUB, Argentina
Instituto Medico Especializado_Capital Federal, Ciudad de Buenos Aires, Buenos Aires, C1405CWB, Argentina
Instituto de Investigaciones Metabolicas (IDIM), Buenos Aires, C1012AAR, Argentina
OMI- Organización Médica de Investigación, Buenos Aires, C1015, Argentina
CICEMO- Consultorio de Investigación Clínica EMO, Buenos Aires, C1405BUB, Argentina
CEDIC Centro de Investigación Clínica, CABA, C1060ABA, Argentina
Centro de Investigación Clínica, CABA, C1060ABA, Argentina
Instituto de Investigaciones Clinicas Mar Del Plata, Mar del Plata, B7600FZN, Argentina
CEDIR - Centro de diagnóstico y rehabilitación Santa Fe, Santa Fe, S3000FSO, Argentina
New South Wales
Paratus Clinical, Blacktown, New South Wales, 2148, Australia
Paratus Clinical, Kanwal, New South Wales, 2259, Australia
Hunter Diabetes Centre, Merewether, New South Wales, 2291, Australia
Royal North Shore Hospital, St Leonards, New South Wales, 2065, Australia
Queensland
Townsville University Hospital, Douglas, Queensland, 4814, Australia
University of Sunshine Coast, Morayfield, Queensland, 4506, Australia
Momentum Clinical Research, Taringa, Queensland, 4068, Australia
South Australia
Southern Adelaide Diabetes & Endocrine Services, Oaklands Park, South Australia, 5046, Australia
Victoria
The Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia
Austrials, St Albans, Victoria, 3021, Australia
Momentum Clinical Research, St Albans, Victoria, 3021, Australia
Atlántico
Clinica de la Costa, Barranquilla, Atlántico, 80020, Colombia
Santander Department
FOSCAL, Floridablanca, Santander Department, 681004, Colombia
Cimedical, Barranquilla, 80001, Colombia
UNIENDO, Bogotá, 110111, Colombia
Centro de Investigación en Reumatología y Especialidades Médicas S.A.S. CIREEM S.A.S., Bogotá, 110221, Colombia
Gujarat
Nirmal Hospital Pvt. Ltd., Surat, Gujarat, 395002, India
SSG Hospital, Baroda, Vadodara, Gujarat, 390001, India
Karnataka
Belgaum Diabetes Centre, Belagavi, Karnataka, 590001, India
Kerala
Government Medical College, Kozhikode, Kozhikode, Kerala, 673008, India
Indian Institute of Diabetes, Thiruvnanthapuram, Kerala, 695033, India
Maharashtra
Seth GS Medical College & KEM Hospital, Mumbai, Maharashtra, 400012, India
BSES MG hospital, Mumbai, Maharashtra, 400058, India
Grant Medical Foundation Ruby Hall Clinic, Pune, Maharashtra, 411001, India
Chellaram Diabetes Institute, Pune, Maharashtra, 411021, India
New Delhi
Maulana Azad Medical College, Delhi, New Delhi, 110002, India
Rajasthan
SMS Medical College & Hospital, Jaipur, Rajasthan, 302004, India
Diabetes, Thyroid and Endocrine Centre, Jaipur, Rajasthan, 302006, India
Tamil Nadu
Christian Medical College Hospital, Vellore, Vellore, Tamil Nadu, 632004, India
Telangana
AIG Hospitals,Hyderabad, Hyderabad, Telangana, 500032, India
Uttar Pradesh
Government Institute of Medical Sciences, Noida, Uttar Pradesh, 201310, India
West Bengal
BP Poddar Hospital, Kolkata, West Bengal, 700053, India
Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N Medical College, Aligarh Muslim University, Aligarh, 202002, India
SRM Centre for Clinical Trials & Research, Chennai, 603203, India
Nirmal Hospital Pvt. Ltd., Surat, 395002, India
Jothydev's Diabetes & Research Center, Thriruvananthapuram, 695 032, India
Gauteng
Dr Wilhase's rooms, Boksburg, Gauteng, 1466, South Africa
Ubuntu Clinical Research, Johannesburg, Gauteng, 1827, South Africa
Krugersdorp Medical Centre, Krugersdorp, Gauteng, 1739, South Africa
KwaZulu-Natal
Synapta Clinical Research Centre, Durban, KwaZulu-Natal, 4001, South Africa
Dr J Reddy, Durban, KwaZulu-Natal, 4450, South Africa
Western Cape
Bella Vita Clinical Research, Cape Town, Western Cape, 7560, South Africa
Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, 807, Taiwan
Chung Shan Medical University Hospital, Taichung, 402, Taiwan
Taichung Veterans General Hospital, Taichung, 407, Taiwan
Kuang Tien General Hospital, Taichung, 433, Taiwan
National Cheng Kung University Hospital, Tainan, 704, Taiwan
National Taiwan University Hospital_main, Taipei, 100, Taiwan
Taipei Veterans General Hospital, Taipei, 112, Taiwan