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

Diabetes Mellitus, Type 2 Clinical Trial

— STRIDE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04560998
• Other study ID #: NN9535-4533
• Secondary ID: 2019-003399-38U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 1, 2020
• Est. completion date: July 5, 2024

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 792
• Est. completion date: July 5, 2024
• Est. primary completion date: June 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

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 (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.

Locations

Country	Name	City	State
Austria	Universitätsklinik für Innere Medizin	Graz
Austria	AKH Wien	Wien
Austria	Klinik Landstraße	Wien
Belgium	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
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	North York Diagn & Cardiac Ctr	North York	Ontario
Canada	North York Diagnostic and Cardiac Centre	North York	Ontario
Canada	CHU de Quebec-Universite Laval	Quebec
Canada	Institut universitaire de cardiologie	Quebec
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	The first hospital of Jilin University	Changchun	Jilin
China	Tianjin Union Medicine Centre	Tianjin
China	1st Affiliated Hosp of Xi'an JiaoTong Uni Medical College	Xi'an	Shaanxi
Czechia	CTC Hodonin s.r.o.	Hodonin
Czechia	EDUMED Jaromer	Jaromer
Czechia	Kucera	Ostrava Dubina
Czechia	Diabetologicka ambulance Plzen	Plzen
Czechia	II. interni klinika - klinika kardiologie a angiologie 1. LF	Praha
Denmark	Rigshospitalet Karkirurgisk afd. RK 3111	København Ø
Denmark	Kolding Sygehus Karkirurgi	Kolding
Denmark	Karkirurgisk Afsnit	Viborg
Germany	Kardiologische Praxis	Bad Homburg
Germany	Dr. med. Young Hee Lee Barkey	Bad Oeynhausen
Germany	Kreutzmann	Dresden
Germany	Medizinische Klinik und Poliklinik III/Angiologie	Dresden
Germany	MVZ CCB Frankfurt Und Main-Taunus GbR	Frankfurt
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
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
Greece	"Hygeia" General Hospital of Athens	Athens
Greece	"Laiko" General Hospital of Athens	Athens
Greece	Konstantopouleio G.H. of Athens, "Agia Olga"	Athens
Greece	General Hospital of Chios "Skilitsio"	Chios
Greece	University Hospital of Athens ATTIKON	Haidari-Athens	Attica
Greece	General Hospital of Lamia	Lamia
Greece	'Ippokrateio' General Hospital of Thessaloniki	Thessaloniki
Greece	General Hospital of Thessaloniki "G.Papanikolaou"	Thessaloniki
Hungary	Semmelweis Egyetem Városmajori Szív- és Érgyógyászat	Budapest
Hungary	Szent Imre Egyetemi Oktatókórház Angiológia	Budapest
Hungary	Szent Margit Rendelointézet Nonprofit Kft.	Budapest
Hungary	Coromed SMO Kft.	Pécs
Hungary	Szegedi Tudományegyetem II. sz Belgyógyászati és Kardiológia	Szeged	Csongrád-Csanád
Hungary	Léda Platán Magánklinika	Zalaegerszeg	Zala Megye
India	SP Medical College	Bikaner	Rajasthan
India	Osmania General Hospital	Hyderabad	Telengana
India	Udyaan Health Care	Lucknow	Uttar Pradesh
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	Sir Ganga Ram Hospital	New Delhi
India	Shri B D Mehta Mahavir Heart Institute	Surat	Gujarat
India	Shri B. D. Mehta Mahavir Heart Institute	Surat	Gujarat
Japan	New Tokyo Heart Clinic_Matsudo-shi, Chiba,	Chiba
Japan	Akaicho Clinic	Chiba-shi, Chiba
Japan	Higashi Takarazuka Satoh Hospital	Hyogo
Japan	Takahashi Hospital	Hyogo
Japan	Naka Kinen Clinic	Ibaraki
Japan	Nishiyamado Keiwa Hospital	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
Latvia	Stradini PAD	Riga
Malaysia	Hospital Universiti Sains Malaysia	Kota Bharu	Kelantan
Malaysia	National Heart Institute	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Malaysia	Hospital Queen Elizabeth II	Sabah
Malaysia	University Technology MARA (UiTM) - Puncak Alam	Sungai Buloh	Selangor
Norway	Sørlandet sykehus HF Kristiansand	Kristiansand
Norway	OUS, Aker	Oslo
Poland	Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET	Krakow	Malopolskie
Poland	UniCardia & UniMedica & UniEstetica	Krakow
Poland	Centrum Medyczne OMEDICA	Poznan
Poland	KO-MED Centra Kliniczne Sp. z o.o.	Pulawy
Poland	Gabinety Lekarskie LabMed	Szczecin
Poland	DoktorA	Warszawa
Poland	Centrum Badan Klinicznych	Wroclaw
Spain	Hospital Vithas Sevilla	Castilleja Dela Cuesta Sevilla
Spain	Hospital Reina Sofia	Córdoba
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Virgen de la Macarena	Sevilla
Sweden	Kärlkirurgen/kärllab	Göteborg
Sweden	Kärlmottagningen	Uppsala
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaoshiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Kuang Tien General Hospital	Taichung City
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
Thailand	Phramongkutklao Hospital-cardio	Bangkok
Thailand	Research Institute for Health Sciences, CMU	Chiang Mai
Thailand	Srinagarind Hospital	Muang	Khon Kaen
Thailand	Maharat Nakhon Ratchasima Hospital_Ratchasima	Nakhon Ratchasima
Thailand	Thammasat University Hospital_Pathumthani	Pathumthani
United States	Rocky Mount Reg VA Med-DN	Aurora	Colorado
United States	LOUISIANA HEART Center	Bogalusa	Louisiana
United States	Capital Area Research LLC	Camp Hill	Pennsylvania
United States	Clearwater Cardiovascular Consultants	Clearwater	Florida
United States	Tampa Bay Medical Research	Clearwater	Florida
United States	Endeavor Health Glenbook Hosp	Glenview	Illinois
United States	Northwest Houston Cardiology, P.A.	Houston	Texas
United States	Angel City Research, Inc.	Los Angeles	California
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Aiyan Diabetes Center	Martinez	Georgia
United States	St. Joseph Heritage Healthcare_Mission Viejo	Mission Viejo	California
United States	Cardiovascular Rsrch of NW_IN	Munster	Indiana
United States	Nebraska West Iowa Hlth System	Omaha	Nebraska
United States	Penn Presb Med Ctr	Philadelphia	Pennsylvania
United States	DMI Research	Pinellas Park	Florida
United States	Amicis Centers of Clinical Research	Saint Louis	Missouri
United States	University of South Florida	Tampa	Florida
United States	Selma Medical Associates	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  China,  Czechia,  Denmark,  Germany,  Greece,  Hungary,  India,  Japan,  Latvia,  Malaysia,  Norway,  Poland,  Spain,  Sweden,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Change in glycosylated haemoglobin (HbA1c)	Percentage point	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in body weight	Kilogram	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in systolic blood pressure	mmHg	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in total cholesterol	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in Low-density lipoprotein (LDL)- cholesterol	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in High density lipoprotein (HDL)- cholesterol	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in triglycerides	Ratio to baseline	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in ankle-brachial index (ABI)	Ratio	From screening (week -2) to end of treatment (week 52)
Secondary	Change in toe-brachial index (TBI)	Ratio	From screening (week -2) to end of treatment (week 52)
Secondary	Change in Walking Impairment Questionnaire (WIQ) global score	Percentage point	From baseline (week 0) to end of treatment (week 52)
Secondary	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)