- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04286399
Asian Diabetes Outcomes Prevention Trial (ADOPT)
Study Overview
Status
Conditions
Detailed 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
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Serene Ng Miss
- Phone Number: 67042232
- Email: serene.ng.b.l@singhealth.com.sg
Study Contact Backup
- Name: Salma Asali Miss
- Phone Number: 67042303
- Email: asali.salma@singhealth.com.sg
Study Locations
-
-
-
Singapore, Singapore, 169608
- Recruiting
- Singapore General Hospital (SGH)
-
Contact:
- Serene Ng, Ms
- Phone Number: (+65) 6704 2232
- Email: serene.ng.b.l@singhealth.com.sg
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Intensive Treatment Group
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.
|
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.
Other Names:
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.
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.
Other Names:
|
No Intervention: Control Group
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Combined endpoint based on the first occurrence of cardiovascular death or major adverse cardiovascular event
Time Frame: 48 months
|
Stroke/myocardial infarction/heart failures events
|
48 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Carolyn Lam Prof, National Heart Centre Singapore
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Cardiovascular Diseases
- Diabetes Mellitus
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Vasoconstrictor Agents
- Sodium-Glucose Transporter 2 Inhibitors
- Adrenergic beta-Antagonists
- Angiotensin II
- Angiotensin-Converting Enzyme Inhibitors
- Angiotensin Receptor Antagonists
Other Study ID Numbers
- ADOPT169609
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cardiovascular Diseases
-
Medical College of WisconsinRecruitingCardiovascular Diseases | Cardiovascular Risk Factor | Cardiovascular HealthUnited States
-
Hospital Mutua de TerrassaCompleted
-
Oregon Health and Science UniversityCompletedCardiovascular Disease | Cardiovascular Risk FactorsUnited States
-
Women's College HospitalUniversity Health Network, Toronto; Sunnybrook Health Sciences Centre; Brigham... and other collaboratorsUnknownCARDIOVASCULAR DISEASESCanada, United States
-
Groupe Hospitalier Paris Saint JosephTerminatedCARDIOVASCULAR DISEASESFrance
-
University of FloridaUniversity of Alabama at Birmingham; Brown UniversityCompletedCardiovascular Disease | Psychosocial Influence on Cardiovascular DiseaseUnited States
-
Nanjing Medical UniversityRecruiting
-
Centre Hospitalier Universitaire de la RéunionRecruitingCardiovascular DiseaseFrance
-
National Heart, Lung, and Blood Institute (NHLBI)RecruitingCardiovascular DiseaseUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)RecruitingCardiovascular DiseaseUnited States
Clinical Trials on Renin-angiotensin-aldosterone system inhibitors
-
Université de SherbrookeFoundation of the StarsRecruitingPrimary Hyperaldosteronism | Hypertensive Disorder of PregnancyCanada
-
Centre Hospitalier Universitaire DijonCompleted
-
Changi General HospitalCompletedStroke | Primary AldosteronismSingapore
-
University of Sao PauloTerminatedCovid19 | Angiotensin II Receptor Antagonist Adverse ReactionBrazil
-
Shanghai Chest HospitalNot yet recruitingCardiac Event | Immune Checkpoint Inhibitor | Adverse Reactions | Non-Small Cell Lung Cancer Patients
-
Chulalongkorn UniversityCompletedHeart Failure With Reduced Ejection Fraction
-
Qifu LiFu Wai Hospital, Beijing, ChinaCompletedHyperaldosteronism; Primary | Hypertension SecondaryChina
-
Fundación Centro Nacional de Investigaciones Cardiovasculares...London School of Hygiene and Tropical Medicine; Ferrer Internacional S.A.; Charite... and other collaboratorsCompletedMyocardial Infarction | Cardiovascular DiseaseSpain, Germany, France, Czechia, Hungary, Italy, Poland
-
Assistance Publique - Hôpitaux de ParisActive, not recruiting
-
Wonju Severance Christian HospitalRecruitingHeart Failure | MortalityKorea, Republic of