A Research Study to Compare a Medicine Called Semaglutide Against Placebo in People With Peripheral Arterial Disease and Type 2 Diabetes (STRIDE)

Effects of Semaglutide on Functional Capacity in Patients With Type 2 Diabetes and Peripheral Arterial Disease

This study is done to see if semaglutide has an effect on walking ability compared with placebo (dummy medicine) in people with peripheral arterial disease (PAD) and type 2 diabetes. Participants will either get semaglutide or placebo ("dummy") medicine - which treatment participants get is decided by chance. Semaglutide is a medicine for type 2 diabetes that can be prescribed by doctors in some countries. Participants will get the study medicine (semaglutide or placebo) in a pre-filled pen for injection. Participants must inject it once a week into the stomach area, thigh, or upper arm, at any time of the day. The study will last for about 59 weeks. Participants will have 8 clinic visits and 1 phone call with the study doctor. At some clinic visits, participants will have blood tests. At some visits participants will also do a treadmill test to measure how far they can walk. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 2; Peripheral Arterial Disease
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 792
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Austria
  • Graz, Austria, 8036
    • Universitätsklinik für Innere Medizin
  • Innsbruck, Austria, 6020
    • Univ.-Klinik für Innere Medizin III
  • Wien, Austria, 1090
    • AKH Wien
  • Wien, Austria, 1030
    • Klinik Landstraße
• Belgium
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis Bonheiden - Thoracic and Vascular Surgery
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg AV - Thoracic
  • Gent, Belgium, 9000
    • UZ Gent - Thoracale Vasculaire Heelkunde
  • Gent, Belgium, 9000
    • UZ Gent_Gent_1
  • Kortrijk, Belgium, 8500
    • AZ Groeninge - Thoracic Vascular Surgery
  • Leuven, Belgium, 3000
    • UZ Leuven - Hart en Vaatziekten
• Canada
  • Quebec, Canada, G1L 3L5
    • CHU de Quebec-Universite Laval
  • Quebec, Canada, G1V 4G5
    • Institut universitaire de cardiologie
  • Ontario
    • North York, Ontario, Canada, M6B 3H7
      • North York Diagnostic and Cardiac Centre
    • North York, Ontario, Canada, M6B 3H7
      • North York Diagn & Cardiac Ctr
  • Quebec
    • Brossard, Quebec, Canada, J4Z 2K9
      • ViaCar Recherche Clinique Inc
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Montreal, Quebec, Canada, H1T 3Y7
      • Clinique Sante Cardio MC
    • Montreal, Quebec, Canada, QC H1T 1C8
      • Montreal Heart Institute
• China
  • Tianjin, China, 300121
    • Tianjin Union Medicine Centre
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital Capital Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • 1st Affiliated Hosp of Xi'an JiaoTong Uni Medical College
• Czechia
  • Hodonin, Czechia, 695 01
    • CTC Hodonin s.r.o.
  • Jaroměř, Czechia, 55101
    • EDUMED Jaromer
  • Ostrava Dubina, Czechia, 700 30
    • Kucera
  • Plzen, Czechia, 30100
    • Diabetologicka ambulance Plzen
  • Praha, Czechia, 128 08
    • II. interni klinika - klinika kardiologie a angiologie 1. LF
• Denmark
  • Kolding, Denmark, 6000
    • Kolding Sygehus Karkirurgi
  • København Ø, Denmark, 2100
    • Rigshospitalet Karkirurgisk afd. RK 3111
  • Viborg, Denmark, 8800
    • Karkirurgisk Afsnit
• Germany
  • Bad Homburg, Germany, 61348
    • Kardiologische Praxis
  • Bad Oeynhausen, Germany, 32545
    • Dr. med. Young Hee Lee Barkey
  • Dresden, Germany, 01277
    • Kreutzmann
  • Dresden, Germany, 01307
    • Medizinische Klinik und Poliklinik III/Angiologie
  • Frankfurt, Germany, 60389
    • MVZ CCB Frankfurt Und Main-Taunus GbR
  • Lübeck, Germany, 23562
    • Universitätsklinikum Schleswig-Holstein
  • Münster, Germany, 48145
    • Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
  • Nürnberg, Germany, 90402
    • Gemeinschaftspraxis Haggenmiller/Jeserich
  • Saint Ingbert-Oberwürzbach, Germany, 66386
    • Zentrum für klinische Studien Alexander Segner
• Greece
  • Athens, Greece, GR-11527
    • "Laiko" General Hospital of Athens
  • Athens, Greece, GR-14233
    • Konstantopouleio G.H. of Athens, "Agia Olga"
  • Athens, Greece, GR-15123
    • "Hygeia" General Hospital of Athens
  • Chios, Greece, GR82100
    • General Hospital of Chios "Skilitsio"
  • Haidari-Athens, Greece, GR-12462
    • University Hospital of Athens ATTIKON
  • Lamia, Greece, GR35100
    • General Hospital of Lamia
  • Thessaloniki, Greece, GR-57010
    • General Hospital of Thessaloniki "G.Papanikolaou"
  • Thessaloniki, Greece, GR 54642
    • 'Ippokrateio' General Hospital of Thessaloniki
• Hungary
  • Budapest, Hungary, 1032
    • Szent Margit Rendelőintézet Nonprofit Kft.
  • Budapest, Hungary, 1115
    • Szent Imre Egyetemi Oktatókórház Angiológia
  • Budapest, Hungary, 1122
    • Semmelweis Egyetem Városmajori Szív- és Érgyógyászat
  • Pécs, Hungary, 7623
    • Coromed SMO Kft.
  • Csongrád-Csanád
    • Szeged, Csongrád-Csanád, Hungary, 6725
      • Szegedi Tudományegyetem II. sz Belgyógyászati és Kardiológia
  • Zala Megye
    • Zalaegerszeg, Zala Megye, Hungary, 8900
      • Léda Platán Magánklinika
• India
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
  • Gujarat
    • Surat, Gujarat, India, 395001
      • Shri B D Mehta Mahavir Heart Institute
    • Surat, Gujarat, India, 395001
      • Shri B. D. Mehta Mahavir Heart Institute
  • Maharashtra
    • Nagpur, Maharashtra, India, 440012
      • Shri Krishna Hrudayalaya & Critical Care Centre
    • Nagpur, Maharashtra, India, 440012
      • Shrikrishna Hrudayalaya and Critical Care Centre
    • Nashik, Maharashtra, India, 422005
      • Vijan Hospital & Research Centre
  • Rajasthan
    • Bikaner, Rajasthan, India, 334003
      • SP Medical College
  • Telengana
    • Hyderabad, Telengana, India, 500 012
      • Osmania General Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226002
      • Udyaan Health Care
• Japan
  • Chiba, Japan, 271-0077
    • New Tokyo Heart Clinic_Matsudo-shi, Chiba,
  • Chiba-shi, Chiba, Japan, 260-0804
    • Akaicho Clinic
  • Hyogo, Japan, 654-0026
    • Takahashi Hospital
  • Hyogo, Japan, 665-0873
    • Higashi Takarazuka Satoh Hospital
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic
  • Ibaraki,, Japan, 331-0133
    • Nishiyamado Keiwa Hospital
  • Omihachiman-shi, Siga, Japan, 523-0082
    • Omihachiman Community Medical Center_Omihachiman-shi, Siga
  • Osaka, Japan, 559-0012
    • Minamiosaka Hospital
  • Saitama, Japan, 360-0197
    • Saitama Cardiovascular and Respiratory Center
  • Shiga, Japan, 525-8585
    • Omi Medical Center
  • Tokyo, Japan, 192-0918
    • Minamino Cardiovascular Hospital
• Latvia
  • Riga, Latvia, LV-1002
    • Stradini PAD
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • National Heart Institute
  • Sabah, Malaysia, 88300
    • Hospital Queen Elizabeth II
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 16150
      • Hospital Universiti Sains Malaysia
  • Pahang
    • Kuantan, Pahang, Malaysia, 25100
      • Hospital Tengku Ampuan Afzan
  • Selangor
    • Sungai Buloh, Selangor, Malaysia, 47000
      • University Technology MARA (UiTM) - Puncak Alam
  • Wilayah Persekutuan Kuala Lumpur
    • Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
• Norway
  • Kristiansand, Norway, 4615
    • Sørlandet sykehus HF Kristiansand
  • Oslo, Norway, 0586
    • OUS, Aker
• Poland
  • Krakow, Poland, 31-271
    • UniCardia & UniMedica & UniEstetica
  • Poznan, Poland, 60-111
    • Centrum Medyczne OMEDICA
  • Pulawy, Poland, 24-100
    • KO-MED Centra Kliniczne Sp. z o.o.
  • Szczecin, Poland, 71-531
    • Gabinety Lekarskie LabMed
  • Warszawa, Poland, 05-077
    • DoktorA
  • Wroclaw, Poland, 51-162
    • Centrum Badan Klinicznych
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-261
      • Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET
• Spain
  • Castilleja Dela Cuesta Sevilla, Spain, 41950
    • Hospital Vithas Sevilla
  • Córdoba, Spain, 14004
    • Hospital Reina Sofía
  • Madrid, Spain, 28009
    • Hospital Gregorio Marañon
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Sevilla, Spain, 41009
    • Hospital Virgen de la Macarena
• Sweden
  • Göteborg, Sweden, 413 45
    • Kärlkirurgen/kärllab
  • Uppsala, Sweden, 751 85
    • Kärlmottagningen
• Taiwan
  • Kaoshiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taichung City, Taiwan, 433
    • Kuang Tien General Hospital
  • Tainan City, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taoyuan city, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou Branch
• Thailand
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital-cardio
  • Chiang Mai, Thailand, 50200
    • Research Institute for Health Sciences, CMU
  • Nakhon Ratchasima, Thailand, 30000
    • Maharat Nakhon Ratchasima Hospital_Ratchasima
  • Pathumthani, Thailand, 12120
    • Thammasat University Hospital_Pathumthani
  • Khon Kaen
    • Muang, Khon Kaen, Thailand, 40002
      • Srinagarind Hospital
• United States
  • California
    • Los Angeles, California, United States, 90010
      • Angel City Research, Inc.
    • Mission Viejo, California, United States, 92691
      • St. Joseph Heritage Healthcare_Mission Viejo
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Rocky Mount Reg VA Med-DN
  • Florida
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular Consultants
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research
    • Pinellas Park, Florida, United States, 33782
      • DMI Research
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Martinez, Georgia, United States, 30907
      • Aiyan Diabetes Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health
  • Indiana
    • Munster, Indiana, United States, 46321
      • Cardiovascular Rsrch of NW_IN
  • Louisiana
    • Bogalusa, Louisiana, United States, 70427
      • Louisiana Heart Center
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Amicis Centers of Clinical Research
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Nebraska West Iowa Hlth System
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Cardio Assoc
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presb Med Ctr
  • Texas
    • Houston, Texas, United States, 77070
      • Northwest Houston Cardiology, P.A.
    • Lubbock, Texas, United States, 79430-8183
      • Texas Tech University Health Science Center
  • Virginia
    • Winchester, Virginia, United States, 22601-3834
      • Selma Medical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan: Male or female, age above or equal to 20 years at time of signing informed consent
• Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.

• Symptomatic PAD with intermittent claudication corresponding to Fontaine stage IIa (Rutherford classification grade I, category 1 and 2) meeting all of the following:

  1. Stable symptoms of PAD with intermittent claudication in Fontaine stage IIa (able to walk without stopping more than 200 m/656 feet/2 blocks) for at least 90 days prior to the day of screening based on patient interview.
  2. Screening flat treadmill test (3.2 km/h (2 mph)): Pain-free walking distance of at least 200 meters/656 feet.
  3. Screening constant load treadmill test with fixed inclination of 12% and a fixed speed of 3.2 km/h (2 mph): Walking distance equal to or less than 600 meters/1968 feet.
  4. Ankle-brachial-index (ABI) equal to or below 0.90 or toe-brachial index (TBI) equal to or below 0.7 (the leg with lowest index is chosen in case of bilateral disease).

Exclusion Criteria:

• Current or previous treatment with any GLP-1 receptor agonist (GLP-1-RA) within 90 days prior to the day of screening.
• Walking ability limited by conditions other than PAD (e.g. aortic aneurism, dysregulated arrhythmia or hypertension, angina pectoris, heart failure, chronic obstructive or restrictive pulmonary disease, Parkinson's disease, severe peripheral neuropathy, amputations, wheel chair or walker dependency, osteoarthritis, morbid obesity, severe varicose veins, etc.).
• Planned orthopaedic surgery in the legs, or other major surgery known on the day of screening (surgery affecting walking ability).
• Vascular revascularisation procedure of any kind 180 days prior to the day of screening.
• Planned arterial revascularisation known on the day of screening.
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within 180 days prior to the day of screening.
• Heart failure presently classified as being in New York Heart Association (NYHA) class III-IV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Semaglutide given in addition to standard-of-care treatment	Drug: Semaglutide; Semaglutide is administered subcutaneously (s.c.; under the skin) once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.
Placebo Comparator: Placebo (semaglutide); Placebo given in addition to standard-of-care treatment	Drug: Placebo (semaglutide); Placebo (semaglutide) is administered s.c. once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maximum walking distance on a constant load treadmill test	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain-free walking distance on a constant load treadmill test	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score	Score on a scale. Vascular Quality of Life 6 (VascuQoL): A shorter version of the standardized, validated questionnaire, VascuQoL-25 which is used to evaluate vascular disease-specific health outcomes. VascuQol total score includes scores of Activity Domain, Symptom Domain, Pain Domain, Emotional Domain and Social Domain. Each item is rated as a 4 point response scale, with a score of 1 being the worst and a score of 4 the best possible. The total score is the sum of all 6 items scores. Each question relates to a separate domain, with a highest score of 4 which indicates best health outcome. The VascuQoL-6 is aimed specifically at PAD patients	From baseline (week 0) to end of treatment (week 52)
Follow-up change in maximum walking distance on a constant load treadmill test	Ratio to baseline	From baseline (week 0) to end of follow-up (week 57)
Follow-up change in pain-free walking distance on a constant load treadmill test	Ratio to baseline	From baseline (week 0) to end of follow-up (week 57)
Change in glycosylated haemoglobin (HbA1c)	Percentage point	From baseline (week 0) to end of treatment (week 52)
Change in body weight	Kilogram	From baseline (week 0) to end of treatment (week 52)
Change in systolic blood pressure	mmHg	From baseline (week 0) to end of treatment (week 52)
Change in total cholesterol	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Change in Low-density lipoprotein (LDL)- cholesterol	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Change in High density lipoprotein (HDL)- cholesterol	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Change in triglycerides	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Change in ankle-brachial index (ABI)	Ratio	From screening (week -2) to end of treatment (week 52)
Change in toe-brachial index (TBI)	Ratio	From screening (week -2) to end of treatment (week 52)
Change in Walking Impairment Questionnaire (WIQ) global score	Percentage point	From baseline (week 0) to end of treatment (week 52)
Change in Short Form 36 (SF-36) physical functioning domain	Score on a scale. Short form (SF)-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health, of which will be summarised into a physical health. The physical score ranges from 24-101(where higher scores indicate a better physical capability). The domain scores will then be transformed into norm-based scores. At least seven domains must have valid data in order to calculate the physical health. To calculate physical health, the physical domain must be one of these seven domains. These scores will be summarised by domains and component summary scores by treatment and visit. A positive change in score indicates an improvement since baseline	From baseline (week 0) to end of treatment (week 52)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): June 5, 2024
• Study Completion (Estimated): July 5, 2024

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 23, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Atherosclerosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Peripheral Arterial Disease; Peripheral Vascular Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: NN9535-4533; 2019-003399-38 (Registry Identifier: European Medicines Agency (EudraCT)); U1111-1238-7071 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No