A Study of Cardiovascular Events iN Diabetes Plus (ASCEND PLUS)

ASCEND PLUS is testing whether, for people with type 2 diabetes who have not previously had a heart attack or stroke, regularly taking a tablet called semaglutide can safely help to reduce heart attacks, strokes, mini-strokes, the need for any procedures to unblock or bypass an artery to their heart, and the chance of dying because of vascular problems.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Semaglutide Oral Tablet; Drug: Placebo oral tablet

Detailed Description

ASCEND PLUS aims to assess the effects of the GLP1 receptor agonist, oral semaglutide, on major adverse cardiovascular events in people with type 2 diabetes who have not previously suffered a heart attack or stroke. The study will be conducted using novel, streamlined methodology. Participants will be identified from centrally held routinely collected NHS healthcare datasets and invited to join the trial. There will be no physical sites, and all interactions with participants will be conducted directly using innovative patient-centred web-based technology, supplemented by telephone, video call contact and mailed letters.

Study treatment will be mailed to participants. Information regarding serious adverse events and study outcomes relevant to patients with type 2 diabetes mellitus will be collected by regular linkage to UK National Health Service health records both during the scheduled treatment period and for the subsequent 20 years' long term follow-up after the scheduled treatment period.

The trial design includes an active run-in phase, prior to randomisation, during which participants will be asked to take 4-weeks of active 3mg oral semaglutide followed by 4 to 8-weeks of active 7mg oral semaglutide daily.

Participants who are randomised will be allocated to receive either 14mg oral semaglutide or matching placebo daily during the scheduled treatment period. There will be the opportunity to reduce the dose to 7mg or matching placebo if required.

The scheduled treatment period, during which participants are requested to take the study treatment and complete follow-up assessments, is anticipated to continue until the required number of participants has experienced a primary outcome following randomisation. This is expected to occur at a median of approximately 5 years after randomisation.

• Study Type: Interventional
• Enrollment (Anticipated): 20000
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom
    • Recruiting
    • Clinical Trial Service Unit and Epidemiological Studies Unit
    • Contact: David Preiss

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged at least 55 years at the time of the Screening assessment
• Type 2 Diabetes Mellitus (based on self-reported medical history)

Exclusion criteria:

• Myocardial Infarction
• Stroke
• Current or planned treatment with a GLP-1 RA
• Previous hypersensitivity to or intolerance of GLP-1 RA therapy
• Severe hypoglycaemia within the last six months or during run-in
• Symptomatic hypoglycaemia within the last month
• Currently under consideration to commence insulin
• Severe heart failure (NYHA class 4)
• Current or planned renal replacement therapy
• Unwilling to complete regular follow-up assessments
• Ongoing treatment for cancer or diagnosis with cancer (excluding non-melanoma skin cancer) in the last 2 years
• Type 1 or other type of diabetes (e.g. MODY)
• History of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Currently breastfeeding or pregnant, or planning a pregnancy
• Any serious illness which is likely to limit survival or active participation for at least 5 years
• Current participation in a clinical trial with an unlicensed investigational medicinal product used to treat diabetes
• For participants taking thyroxine, lack of agreement to arrange a thyroid function test in the next 3 months and agree to regular testing throughout the trial
• Non-adherence to run-in treatment (i.e. reports taking the run-in tablets 'Never' or 'Only occasionally')
• Their doctor does not wish them to be randomised

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo oral tablet; Placebo oral semaglutide
Active Comparator: Oral semaglutide; 14mg daily (option to reduce to 7mg daily)	Drug: Semaglutide Oral Tablet; Oral semaglutide 14mg daily (option to reduce to 7mg daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE+)	MACE+ is an expanded composite, defined as: Death from cardiovascular disease; Non-fatal myocardial infarction; Non-fatal stroke; Transient ischaemic attack; Coronary revascularisation	Scheduled treatment period (anticipated median follow-up period of 5-years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE)	MACE is a composite, defined as: Death from cardiovascular disease; Non-fatal myocardial infarction; Non-fatal stroke	Scheduled treatment period (anticipated median follow-up period of 5-years)

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Anticipated): August 17, 2028
• Study Completion (Anticipated): August 17, 2048

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CTSU_ASCEND-PLUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Proposals for substudies must be approved by the Steering Committee.
• IPD Sharing Time Frame: After publication of results
• IPD Sharing Access Criteria: Procedures for accessing the data for this study are available on: https://www.ndph.ox.ac.uk/data-access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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