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

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 2; Peripheral Arterial Disease
• Interventions: Drug: Semaglutide; Drug: Placebo (semaglutide)

• Registration Number: NCT04560998
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-18
• Study First Submitted QC: 2020-09-18
• Study First Posted: 2020-09-23
• Study Start: 2020-10-01
• Primary Completion: 2024-06-05
• Study Completion: 2024-07-12
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-02
• Last Update Posted: 2025-01-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 792

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide	Semaglutide	Semaglutide given in addition to standard-of-care treatment
Placebo (semaglutide)	Placebo (semaglutide)	Placebo given in addition to standard-of-care treatment

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Low-density lipoprotein (LDL)- cholesterol	From baseline (week 0) to end of treatment (week 52)	Ratio to baseline
Change in High density lipoprotein (HDL)- cholesterol	From baseline (week 0) to end of treatment (week 52)	Ratio to baseline
Follow-up change in maximum walking distance on a constant load treadmill test	From baseline (week 0) to end of follow-up (week 57)	Ratio to baseline
Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score	From baseline (week 0) to end of treatment (week 52)	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
Change in pain-free walking distance on a constant load treadmill test	From baseline (week 0) to end of treatment (week 52)	Ratio to baseline
Follow-up change in pain-free walking distance on a constant load treadmill test	From baseline (week 0) to end of follow-up (week 57)	Ratio to baseline
Change in glycosylated haemoglobin (HbA1c)	From baseline (week 0) to end of treatment (week 52)	Percentage point
Change in body weight	From baseline (week 0) to end of treatment (week 52)	Kilogram
Change in systolic blood pressure	From baseline (week 0) to end of treatment (week 52)	mmHg
Change in total cholesterol	From baseline (week 0) to end of treatment (week 52)	Ratio to baseline
Change in triglycerides	From baseline (week 0) to end of treatment (week 52)	Ratio to baseline
Change in Walking Impairment Questionnaire (WIQ) global score	From baseline (week 0) to end of treatment (week 52)	Percentage point
Change in ankle-brachial index (ABI)	From screening (week -2) to end of treatment (week 52)	Ratio
Change in toe-brachial index (TBI)	From screening (week -2) to end of treatment (week 52)	Ratio
Change in Short Form 36 (SF-36) physical functioning domain	From baseline (week 0) to end of treatment (week 52)	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

Trial Locations

Locations (122)

The First Affiliated Hospital of Xi'an Jiaotong University-Cardiovascular; 🇨🇳 Xi'an, Shaanxi, China

Tianjin Union Medical Center-Cardiology; 🇨🇳 Tianjin, China

Angel City Research, Inc.; 🇺🇸 Los Angeles, California, United States

St. Joseph Heritage Healthcare_Mission Viejo; 🇺🇸 Mission Viejo, California, United States

Rocky Mount Reg VA Med-DN; 🇺🇸 Aurora, Colorado, United States

Clearwater Cardiovascular Consultants; 🇺🇸 Clearwater, Florida, United States

Tampa Bay Medical Research; 🇺🇸 Clearwater, Florida, United States

DMI Research; 🇺🇸 Pinellas Park, Florida, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Aiyan Diabetes Center; 🇺🇸 Martinez, Georgia, United States

Endeavor Health Glenbook Hosp; 🇺🇸 Glenview, Illinois, United States

Cardiovascular Rsrch of NW_IN; 🇺🇸 Munster, Indiana, United States

LOUISIANA HEART Center; 🇺🇸 Covington, Louisiana, United States

Amicis Centers of Clinical Research; 🇺🇸 Saint Louis, Missouri, United States

Nebraska West Iowa Hlth System; 🇺🇸 Omaha, Nebraska, United States

Capital Area Research LLC; 🇺🇸 Camp Hill, Pennsylvania, United States

Penn Presb Med Ctr; 🇺🇸 Philadelphia, Pennsylvania, United States

Northwest Houston Cardiology, P.A.; 🇺🇸 Houston, Texas, United States

Texas Tech University Health Science Center; 🇺🇸 Lubbock, Texas, United States

Selma Medical Associates; 🇺🇸 Winchester, Virginia, United States

Universitätsklinik für Innere Medizin Graz; 🇦🇹 Graz, Austria

Klinik Landstraße; 🇦🇹 Wien, Austria

AKH Wien; 🇦🇹 Wien, Austria

Imeldaziekenhuis Bonheiden - Thoracic and Vascular Surgery; 🇧🇪 Bonheiden, Belgium

Ziekenhuis Oost-Limburg AV - Thoracic; 🇧🇪 Genk, Belgium

UZ Gent - Thoracale Vasculaire Heelkunde; 🇧🇪 Gent, Belgium

UZ Gent_Gent_1; 🇧🇪 Gent, Belgium

AZ Groeninge - Thoracic Vascular Surgery; 🇧🇪 Kortrijk, Belgium

UZ Leuven - Hart en Vaatziekten; 🇧🇪 Leuven, Belgium

North York Diagn & Cardiac Ctr; 🇨🇦 North York, Ontario, Canada

North York Diagnostic and Cardiac Centre; 🇨🇦 North York, Ontario, Canada

ViaCar Recherche Clinique Inc; 🇨🇦 Brossard, Quebec, Canada

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Clinique Sante Cardio MC; 🇨🇦 Montreal, Quebec, Canada

Montreal Heart Institute; 🇨🇦 Montreal, Quebec, Canada

CHU de Quebec-Universite Laval; 🇨🇦 Quebec, Canada

Institut universitaire de cardiologie; 🇨🇦 Quebec, Canada

Xuanwu Hospital Capital Medical University; 🇨🇳 Beijing, Beijing, China

The first hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

1st Affiliated Hosp of Xi'an JiaoTong Uni Medical College; 🇨🇳 Xi'an, Shaanxi, China

Tianjin Union Medicine Centre; 🇨🇳 Tianjin, China

CTC Hodonin s.r.o.; 🇨🇿 Hodonin, Czechia

EDUMED Jaromer; 🇨🇿 Jaroměř, Czechia

Kucera; 🇨🇿 Ostrava Dubina, Czechia

Diabetologicka ambulance Plzen; 🇨🇿 Plzen, Czechia

Kolding Sygehus Karkirurgi; 🇩🇰 Kolding, Denmark

Rigshospitalet Karkirurgisk afd. RK 3111; 🇩🇰 København Ø, Denmark

Karkirurgisk Afsnit; 🇩🇰 Viborg, Denmark

Kardiologische Praxis; 🇩🇪 Bad Homburg, Germany

Herz- und Diabeteszentrum NRW - Bad Oeynhausen; 🇩🇪 Bad Oeynhausen, Germany

Kreutzmann; 🇩🇪 Dresden, Germany

Medizinische Klinik und Poliklinik III/Angiologie TU Dresden; 🇩🇪 Dresden, Germany

MVZ CCB Frankfurt Und Main-Taunus GbR; 🇩🇪 Frankfurt, Germany

Institut für Diabetesforschung GmbH Münster - Dr. med. Rose; 🇩🇪 Münster, Germany

Gemeinschaftspraxis Haggenmiller/Jeserich; 🇩🇪 Nürnberg, Germany

Zentrum für klinische Studien Alexander Segner; 🇩🇪 Saint Ingbert-Oberwürzbach, Germany

University Hospital of Athens ATTIKON; 🇬🇷 Haidari-Athens, Attica, Greece

"Laiko" General Hospital of Athens; 🇬🇷 Athens, Greece

Konstantopouleio G.H. of Athens, "Agia Olga"; 🇬🇷 Athens, Greece

"Hygeia" General Hospital of Athens; 🇬🇷 Athens, Greece

General Hospital of Chios "Skilitsio"; 🇬🇷 Chios, Greece

General Hospital of Lamia; 🇬🇷 Lamia, Greece

'Ippokrateio' General Hospital of Thessaloniki; 🇬🇷 Thessaloniki, Greece

Szegedi Tudományegyetem II. sz Belgyógyászati és Kardiológia; 🇭🇺 Szeged, Csongrád-Csanád, Hungary

Léda Platán Magánklinika; 🇭🇺 Zalaegerszeg, Zala Megye, Hungary

Szent Margit Rendelőintézet Nonprofit Kft.; 🇭🇺 Budapest, Hungary

Szent Imre Egyetemi Oktatókórház Angiológia; 🇭🇺 Budapest, Hungary

Semmelweis Egyetem Városmajori Szív- és Érgyógyászat; 🇭🇺 Budapest, Hungary

Coromed SMO Kft.; 🇭🇺 Pécs, Hungary

Shri B D Mehta Mahavir Heart Institute; 🇮🇳 Surat, Gujarat, India

Shri B. D. Mehta Mahavir Heart Institute; 🇮🇳 Surat, Gujarat, India

Shri Krishna Hrudayalaya & Critical Care Centre; 🇮🇳 Nagpur, Maharashtra, India

Shrikrishna Hrudayalaya and critical care centre; 🇮🇳 Nagpur, Maharashtra, India

Vijan Hospital & Research Centre; 🇮🇳 Nashik, Maharashtra, India

SP Medical College; 🇮🇳 Bikaner, Rajasthan, India

Osmania General Hospital; 🇮🇳 Hyderabad, Telangana, India

Udyaan Health Care; 🇮🇳 Lucknow, Uttar Pradesh, India

Sir Ganga Ram Hospital; 🇮🇳 New Delhi, India

Akaicho Clinic; 🇯🇵 Chiba-shi, Chiba, Japan

New Tokyo Heart Clinic_Matsudo-shi, Chiba,; 🇯🇵 Chiba, Japan

Higashi Takarazuka Satoh Hospital; 🇯🇵 Hyogo, Japan

Nishiyamado Keiwa Hospital; 🇯🇵 Ibaraki,, Japan

Naka Kinen Clinic; 🇯🇵 Ibaraki, Japan

Omihachiman Community Medical Center_Omihachiman-shi, Siga; 🇯🇵 Omihachiman-shi, Siga, Japan

Minamiosaka Hospital; 🇯🇵 Osaka, Japan

Saitama Cardiovascular and Respiratory Center; 🇯🇵 Saitama, Japan

Omi Medical Center; 🇯🇵 Shiga, Japan

Minamino Cardiovascular Hospital; 🇯🇵 Tokyo, Japan

Stradini PAD; 🇱🇻 Riga, Latvia

Hospital Universiti Sains Malaysia; 🇲🇾 Kota Bharu, Kelantan, Malaysia

Hospital Tengku Ampuan Afzan; 🇲🇾 Kuantan, Pahang, Malaysia

University Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia

National Heart Institute; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Queen Elizabeth II; 🇲🇾 Sabah, Malaysia

Sørlandet sykehus HF Kristiansand; 🇳🇴 Kristiansand, Norway

OUS, Aker; 🇳🇴 Oslo, Norway

Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET; 🇵🇱 Krakow, Malopolskie, Poland

UniCardia & UniMedica & UniEstetica; 🇵🇱 Krakow, Poland

Centrum Medyczne OMEDICA; 🇵🇱 Poznan, Poland

Velocity Nova Sp. z o.o.; 🇵🇱 Pulawy, Poland

Gabinety Lekarskie LabMed; 🇵🇱 Szczecin, Poland

DoktorA; 🇵🇱 Warszawa, Poland

Centrum Badan Klinicznych; 🇵🇱 Wroclaw, Poland

Hospital Vithas Sevilla; 🇪🇸 Castilleja Dela Cuesta Sevilla, Spain

Hospital Reina Sofia; 🇪🇸 Córdoba, Spain

Hospital Universitario de la Princesa; 🇪🇸 Madrid, Spain

Hospital Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Virgen de la Macarena; 🇪🇸 Sevilla, Spain

Kärlkirurgen/kärllab; 🇸🇪 Göteborg, Sweden

Kärlmottagningen; 🇸🇪 Uppsala, Sweden

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaoshiung, Taiwan

Kuang Tien General Hospital; 🇨🇳 Taichung City, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Medical Foundation - Linkou Branch; 🇨🇳 Taoyuan city, Taiwan

Srinagarind Hospital; 🇹🇭 Muang, Khon Kaen, Thailand

Phramongkutklao Hospital-cardio; 🇹🇭 Bangkok, Thailand

Research Institute for Health Sciences, CMU; 🇹🇭 Chiang Mai, Thailand

Maharat Nakhon Ratchasima Hospital_Ratchasima; 🇹🇭 Nakhon Ratchasima, Thailand

Thammasat University Hospital_Pathumthani; 🇹🇭 Pathumthani, Thailand