NCT04286399

Brief Summary

The aim of this study is to identify patients with DM at high risk of CVD using elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (\>125pg/mL), and (2) intensify therapy using renin-angiotensin system (RAS) antagonists, beta-blockers and sodium glucose co-transporter-2 inhibitors (SGLT2i) for primary prevention of cardiovascular events in this high-risk DM population.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,400

participants targeted

Target at P75+ for phase_4 diabetes-mellitus

Timeline
100mo left

Started Jul 2019

Longer than P75 for phase_4 diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress46%
Jul 2019Jun 2034

Study Start

First participant enrolled

July 1, 2019

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

October 16, 2019

Completed
4 months until next milestone

First Posted

Study publicly available on registry

February 27, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
12 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2034

Expected
Last Updated

April 30, 2021

Status Verified

March 1, 2021

Enrollment Period

3 years

First QC Date

October 16, 2019

Last Update Submit

April 28, 2021

Conditions

Diabetes MellitusCardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

  • Combined endpoint based on the first occurrence of cardiovascular death or major adverse cardiovascular event

    Stroke/myocardial infarction/heart failures events

    48 months

Study Arms (2)

Intensive Treatment Group

OTHER

High dose of RAASi and beta-blockers (unless contraindicated) as well as preferential use of SGLT2i as per local drug label guidelines on top of standard therapy.

Drug: Renin-angiotensin-aldosterone system inhibitorsDrug: Beta blockerDrug: SGLT2 Inhibitor - Sodium Glucose Cotransporter Subtype 2 Inhibitor Product

Control Group

NO INTERVENTION

Standard therapy where the use of SGLT2i at randomization is not encouraged but RAASi and beta-blockers (except for maximal dosage) are allowed. Prescription or up-titration of the study drugs listed under Intensive Treatment is not encouraged. If investigators/treating physicians feel that further prescription or up-titration is required, a thorough justification is mandatory. Unless there is clinically irrefutable reason, every attempt should be made to use other blood pressure lowering drugs than RAASi or beta-blockers, as well as glucose lowering drugs than SGLT2i, in the control group.

Interventions

Renin-angiotensin-aldosterone system inhibitorsDRUG

Research participants in the intensive therapy arm should be strongly encouraged to follow the intensive treatment strategy. Every attempt should be made to up-titrate RAS-antagonists and beta-blockers (max dosage, unless contraindicated) as well as preferentially use SGLT2i (standard dosage, as required) throughout the trial.

Also known as: Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin II receptor blockers (ARBs)
Intensive Treatment Group
Beta blockerDRUG

Research participants in the intensive therapy arm should be strongly encouraged to follow the intensive treatment strategy. Every attempt should be made to up-titrate RAS-antagonists and beta-blockers (max dosage, unless contraindicated) as well as preferentially use SGLT2i (standard dosage, as required) throughout the trial.

Intensive Treatment Group
SGLT2 Inhibitor - Sodium Glucose Cotransporter Subtype 2 Inhibitor ProductDRUG

Research participants in the intensive therapy arm should be strongly encouraged to follow the intensive treatment strategy. Every attempt should be made to up-titrate RAS-antagonists and beta-blockers (max dosage, unless contraindicated) as well as preferentially use SGLT2i (standard dosage, as required) throughout the trial.

Also known as: SGLT2 inhibitors
Intensive Treatment Group

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Type 2 diabetes for at least six months
  • ≥ 40 years of age, men or women
  • No known cardiovascular disease ( defined as known coronary stenosis \> 70%, reduced left ventricular ejection fraction \< 40%, or a history of myocardial infarction/ coronary revascularization/ heart failure hospitalization/ stroke/ prior non-traumatic lower limb amputation or angioplasty)
  • NT-proBNP \> 125 pg/mL
  • Written informed consent

You may not qualify if:

  • History of hypersensitivity to any of the drugs investigated as well as known or suspected contraindications to the study drugs or previous history of intolerance
  • Patients already on a maximum dose of RAASi or beta-blocker
  • History of DM ketoacidosis/Type 1 DM
  • eGFR \< 45ml/min/1.73m2
  • Symptomatic hypotension and/or Visit 1 systolic blood pressure (SBP) \< 100mmHg.
  • Symptomatic bradycardia, high-grade AV blocks (Grade 2 and 3) and/or Visit 1 heart rate (HR) \< 60bpm.
  • Any disease other than diabetes lowering the patient's life expectancy to less than two years.
  • Chronic infections (E.g. chronic cystitis, recurrent urinary tract infections) or malignancies or uncontrolled thyroid disorder or liver disease
  • Systemic treatment with corticosteroids.
  • Pregnant or nursing women
  • Any other clinical condition that might affect patients' safety during trial, at the investigator's discretion.
  • Participation in an investigational drug trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Singapore General Hospital (SGH)

Singapore, 169608, Singapore

RECRUITING

MeSH Terms

Conditions

Diabetes MellitusCardiovascular Diseases

Interventions

Angiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAdrenergic beta-AntagonistsSodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Protease InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesAdrenergic AntagonistsAdrenergic AgentsNeurotransmitter AgentsPhysiological Effects of DrugsHypoglycemic Agents

Study Officials

  • Carolyn Lam Prof

    National Heart Centre Singapore

    STUDY DIRECTOR

Central Study Contacts

Serene Ng Miss

CONTACT

67042232serene.ng.b.l@singhealth.com.sg

Salma Asali Miss

CONTACT

67042303asali.salma@singhealth.com.sg

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 16, 2019

First Posted

February 27, 2020

Study Start

July 1, 2019

Primary Completion

June 30, 2022

Study Completion (Estimated)

June 30, 2034

Last Updated

April 30, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will not share

Locations

SG(1)