Asian Diabetes Outcomes Prevention Trial

  • STATUS
    Recruiting
  • End date
    Jun 30, 2034
  • participants needed
    2400
  • sponsor
    National Heart Centre Singapore
Updated on 10 May 2021
diabetes
cardiovascular disease
stenosis
stroke
heart failure
type 2 diabetes mellitus
myocardial infarction
infarct
coronary revascularization
primary prevention

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.

Description

Rationale

Cardiovascular events are the leading cause of death among patients with diabetes. Early identification of high-risk diabetic (DM) patients for intensification of preventive therapy may prevent cardiovascular events.

Aims

Among biomarker (N-terminal pro-B-type natriuretic peptide, NT-proBNP)-identified high-risk type 2 DM patients without pre-existing cardiovascular disease, to test if intensive preventive therapy (high dose renin-angiotensin-aldosterone system inhibitors [RAASi], beta-blockade, sodium-glucose co-transporter 2 inhibitors [SGLT2i]) may be associated with reduced cardiovascular events compared to standard of care.

Design

Prospective multinational randomized open-label, parallel group, active-controlled, two-arm, long-term morbidity and mortality trial involving 5 Asian regions (Singapore, Malaysia, China, Taiwan, India; estimated 6 sites each) with patients followed for 2 years.

Population

Adults with type 2 DM without 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) and with NT-proBNP > 125 pg/mL

Duration

The goal is to include approximately 2,400 patients. It is estimated that about 3,000 patients with NT-proBNP > 125pg/mL have to be screened. The screen failure rate, for reasons other than NT-proBNP, is anticipated to be approximately 20%. The observation period is planned to last for two years. However, the trial is event driven and will continue until predefined event rate is reached (see sample size calculation). The total trial duration is expected to last for four years (two years of recruitment and a two-year observation period after last patient in). Every patient will remain in the study for two years after randomization.

Visits

Visit 1:

Pre- Screening

Patients who fulfil the first three pre-screening criteria will proceed for NT-proBNP Point-of-Care (POC) testing:

  • Type 2 diabetes for at least 6 months (ADA definition)
  • Informed consent
  • Check Inclusion/exclusion criteria
  • NT-proBNP (assessed through local point of care device) *If the results for NT-proBNP fall > 125pg/mL, the patients will proceed for Full-Screening.

Full- Screening

  • Patient enrolment details
  • Demographic data
  • Patient diary (blood pressure, heart rate, blood glucose) - distribution (optional)
  • Vital signs -pulse rate and blood pressure
  • Height, weight, waist and hip circumference
  • Medical history (DM, cardiovascular, general and behavioural)
  • Routine Blood sampling for local laboratory, collected from medical record, if available
  • Blood collection for Biomarker analysis (Refer to Section 5.3 and Biospecimen manual)
  • Urine sample for Urine Albumin/creatinine ratio, collected from medical record, if available
  • Electronic randomization (Section 2.6)
  • 12-Lead Electrocardiogram (ECG), collected from medical record, if available (For Singapore sites, ECG values are to be acquired, if not available from medical record)
  • EuroQoL questionnaire (EQ-5D-5L)
  • Drug prescription assessment
  • Health service resource utilisation assessment
  • Cardiovascular events assessment
  • Baseline Adverse Events assessment
  • Echocardiography measurements, collected from medical records, if available (all sites)
  • Echocardiography image acquisition (for Singapore and Taiwan sites only - optional)

Interim visits for the treatment group Visit 1-4 is mandatory for all patients, interim visits (between Visits 1-2) only for the intensive treatment group for up-titration of RAASi and beta-blockers and initiation/continuation of SGLT2i. The frequency is up to the treating physician and titration steps. A visit is not mandatory for each titration step.

  • Patient diary - collect for assessment and distribute new (optional)
  • Vital signs -pulse rate and blood pressure
  • Routine blood sampling for local laboratory, collected from medical record, if available
  • Drug prescription assessment for further up-titration
  • Health service resource utilisation assessment
  • Cardiovascular events assessment
  • Adverse Events assessment Note: SBP and heart rate should not permanently decrease below 100mmHg and 60bpm respectively.

Visit 2 (3 months 1 week)

  • Patient diary - collect for assessment and distribute new (optional)
  • Vital signs -pulse rate and blood pressure
  • Routine Blood sampling for local laboratory, collected from medical record, if available
  • Urine sample for Urine Albumin/creatinine ratio, collected from medical record, if available
  • 12-Lead Electrocardiogram (ECG), collected from medical record, if available (For Singapore sites, ECG values are to be acquired, if not available from medical record)
  • Drug prescription assessment1
  • Health service resource utilisation assessment
  • Cardiovascular events assessment
  • Adverse Events assessment

Visit 3 (12 months 2 weeks)

  • Patient diary - collect for assessment and distribute new (optional)
  • NT-proBNP (assessed through local point of care device)
  • Vital signs -pulse rate and blood pressure
  • Height, weight, waist and hip circumference
  • Routine Blood sampling for local laboratory, collected from medical record, if available
  • Blood collection for Biomarker analysis (Refer to Section 5.3 and Biospecimen manual)
  • Urine sample for Urine Albumin/creatinine ratio, collected from medical record, if available
  • 12-Lead Electrocardiogram (ECG), collected from medical record, if available (For Singapore sites, ECG values are to be acquired, if not available from medical record)
  • EuroQoL questionnaire (EQ-5D-5L)
  • Drug prescription assessment1
  • Health service resource utilisation assessment
  • Cardiovascular events assessment
  • Adverse Events assessment
  • Echocardiography image acquisition (for Taiwan only - optional)

Visit 4: End of Study (24 months 2 weeks)

  • Patient diary - collect for assessment and distribute new (optional)
  • Vital signs -pulse rate and blood pressure
  • Height, weight, waist and hip circumference
  • Routine Blood sampling for local laboratory, collected from medical record, if available
  • Urine sample for Urine Albumin/creatinine ratio, collected from medical record, if available
  • 12-Lead Electrocardiogram (ECG), collected from medical record, if available (For Singapore sites, ECG values are to be acquired, if not available from medical record)
  • EuroQoL questionnaire (EQ-5D-5L)
  • Drug prescription assessment
  • Health service resource utilisation assessment
  • Cardiovascular events assessment
  • Adverse Events assessment

Long-term follow-up (LTFU) (36 and 48 months 3 weeks)

  • Follow up through telephone contact or population registry (if access allowed) until completion of the study
  • Long-term cardiovascular events, mortality and hospitalizations.
  • Adverse Events assessment
  • For all patients, irrespective of whether they reach these two LTFU time points, a final follow-up should be performed at the end of study

Details
Condition Diabetes Mellitus, Cardiovascular Disease, Diabetes Prevention, Diabetes Mellitus Types I and II, Diabetes (Pediatric), diabetes mellitus (dm), cardiovascular diseases, cardiovascular disease (cvd), cardiovascular system diseases, cardiovascular disorders
Treatment Beta blocker, Renin-angiotensin-aldosterone system inhibitors, SGLT2 Inhibitor - Sodium Glucose Cotransporter Subtype 2 Inhibitor Product
Clinical Study IdentifierNCT04286399
SponsorNational Heart Centre Singapore
Last Modified on10 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 40 yrs?
Gender: Male or Female
Do you have any of these conditions: Diabetes Mellitus Types I and II or Diabetes Mellitus or Cardiovascular Disease or Diabetes Prevention or Diabetes (Pediatric)?
Do you have any of these conditions: Diabetes Mellitus or cardiovascular disease (cvd) or cardiovascular diseases or Diabetes Mellitus Types I and II or Cardiovascular Disease or cardiova...?
Do you have any of these conditions: cardiovascular diseases or Diabetes Mellitus or cardiovascular disease (cvd) or Diabetes Mellitus Types I and II or Diabetes (Pediatric) or cardiovasc...?
Do you have any of these conditions: Diabetes Mellitus Types I and II or cardiovascular disease (cvd) or Cardiovascular Disease or cardiovascular system diseases or cardiovascular disease...?
Type 2 diabetes for at least six months
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

Exclusion Criteria

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
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