A multinational, randomized open-label, parallel group, active-controlled, two-arm, long-termmorbidity and mortality trial involving intensive preventive therapy (high doserenin-angiotensin-aldosterone system inhibitors [RAASi], beta-blockade, sodium-glucoseco-transporter 2 inhibitors [SGLT2i]) among biomarker (N-terminal pro-B-type natriuretic peptide,NT-proBNP)-identified high risk type 2 DM patients without pre-existing cardiovascular disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 783
- 试验地点
- 7
- 主要终点
- Combined endpoint based on the first occurrence of cardiovascular death or cardiovascular hospitalization.
研究概览
简要总结
This study is a prospective multinational randomized open-label, parallel group, active-controlled, two-arm, long-term morbidity and mortality trial to evaluate safety and efficacy of intensive preventive therapy (high dose of RAS antagonists, high dose of beta-blockers [unless contraindicated] and preferential usage of SGLT2i) compared to standard care among DM patients. without any 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 amputations or angioplasty).
Upon completing full screening for eligibility, patients will be randomized into intensive preventive therapy or control arm at Visit 1. Subjects in the intensive preventive therapy arm alone will have interim visits (between Visits 1- 2) for up-titration of RAASi/beta-blocker (unless contraindicated) and preferential initiation/continuation of SGLT2i. Patients will be assessed (vital signs and blood chemistry) for up to 2 years (Visit 1-4) and subsequently followed up through population register or telephone contact until study is completed (See Section 4.1 on Visit schedule). For patients on intensive arm treatment, physicians are to maintain SGLT2i dosage as well as up titrated/max dose of RAASi and beta-blockers, at their discretion. This is applicable until end of study or end of LTFU, whichever is later. The frequency of follow-up for these patients will be as clinical indicated.
Remarks:
Site - Grant Govt. Medical College and Sir J.J. Group of Hospitals has been closed on 30 Mar 2024. EC has acknowledged site closure notification on 18 Apr 2024. Site EC name is IEC of New Healthcare Nursing Home (EC registration number - ECR/1388/Inst/MH/2020).
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 40.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Type 2 diabetes for at least six months as defined by the American Diabetes Association Standards of Medical Care in Diabetes 2019 criteria and/or receiving anti-diabetic therapy for the established diagnosis.
- •Fasting plasma glucose greater than or equal to 126 mg/dL or 7.0 mmol per L. Fasting is defined as no caloric intake for at least 8hrs, OR.
- •2 hour postprandial glucose greater than or equal to 200 mg per dL or 11.1 mmol per L during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water, OR.
- •A1C greater than or equal to 6.5 percentage 48 mmol per mol. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay, OR,.
- •In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose greater than or equal to 200mg per dL or 11.1 mmol per L in absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples
- •Greater than or equal to 40 years of age, men or women
- •No known cardiovascular disease defined as known coronary stenosis greater than 70%, reduced left ventricular ejection fraction less than 40%, or a history of myocardial infarction or coronary revascularization or heart failure hospitalization or stroke or prior non-traumatic lower limb amputation or angioplasty
- •NT proBNP greater than 100 pg per mL
- •Written informed consent.
排除标准
- •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 to high dose of RAASi or beta-blocker in the absence of any other blood pressure lowering drugs
- •Patients already on a maximum dose of RAASi or beta-blocker
- •History of DM ketoacidosis or Type 1 DM
- •eGFR less than 30ml per min per 1.73m
- •eGFR cut-off as per local approvals for SGLT2 inhibitor use.
- •Results from clinical tests done within 6 months of the visit date can be used.
- •Symptomatic hypotension and/or Visit 1 systolic blood pressure SBP less than 100mmHg
- •Symptomatic bradycardia, high-grade AV blocks Grade 2 and 3 and or Visit 1 heart rate HR less than 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 investigators discretion
- •Participation in an investigational drug trial.
结局指标
主要结局
Combined endpoint based on the first occurrence of cardiovascular death or cardiovascular hospitalization.
时间窗: Visit 1: | Screening, | Interim visits for the Intensive treatment group only, | Visit 2 (3 months ± 1 week), | Visit 3 (12 months ± 2 weeks), | Visit 4 (24 months ± 2 weeks), | Long-term follow-up (LTFU) (36 and 48 months ± 3 weeks).
Primary
时间窗: Visit 1: | Screening, | Interim visits for the Intensive treatment group only, | Visit 2 (3 months ± 1 week), | Visit 3 (12 months ± 2 weeks), | Visit 4 (24 months ± 2 weeks), | Long-term follow-up (LTFU) (36 and 48 months ± 3 weeks).
次要结局
- Secondary efficacy variables(1) Cardiovascular hospitalization)