Comparative Efficacy of Amlodipine Folic Acid Vs. Amlodipine on the Risk of First Ischemic Stroke Among Participants with Hypertension and MTHFR 677 TT Genotype: a Multi-center, Randomized, Double-blind, Triple-dummy, Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24,000
- 试验地点
- 20
- 主要终点
- First ischemic stroke
研究概览
简要总结
This is a multi-center, randomized, double-blind, triple-dummy, controlled trial in 24,000 Chinese men and women with hypertension and MTHFR 677 TT genotype.
The study participants will be randomized to one of the three treatment groups:
Group A: amlodipine tablet (5mg), taken orally, once daily, serving as active comparator.
Group B: amlodipine folic acid 5.8mg tablet (5mg amlodipine and 0.8mg folic acid), taken orally, once daily.
Group C: amlodipine folic acid 5.8mg tablet plus 5-methyltetrahydrofolate (5-MTHF, 0.4mg), taken orally, once daily.
The primary endpoint is first ischemic stroke.
详细描述
This study consists of 3 periods: Screening, Run-in, and Randomized treatment.
Period I: Screening (V0)
The purpose of Period I is to obtain informed consent and screen for eligible participants.
After obtaining written informed consent, at the screening visit (V0), participants will complete a face-to-face interview and clinical evaluation and measurements. Their biological samples will be collected for laboratory analyses. Collectively, these information will help to determine eligibility for inclusion in the study.
Period II: Run-in Period (VD)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women, aged ≥45 and <75 years.
- •Hypertension: Previously diagnosed with primary hypertension and has been taking antihypertensive medication within the past two weeks; OR has not been taking antihypertensive medications within the last two weeks, but meets the following criteria for hypertension: SBP≥140 mmHg and/or DBP≥90 mmHg (average of at least 2 measurements each time) at two separate (not on the same day) clinical visits.
- •MTHFR 677 TT genotype (based on the test results from the central laboratory during the screening period or a previous official test report from a laboratory with medical testing qualifications).
- •Voluntarily participates and has given signed informed consent.
- •Randomized-treatment phase inclusion criteria:
- •Good compliance during the run-in period, and unlikely to discontinue treatment;
- •No stroke or cardiovascular events during the run-in period;
- •The participant voluntarily agrees to continue the study.
排除标准
- •Previously diagnosed secondary hypertension;
- •Previously diagnosed stroke;
- •Previously diagnosed myocardial infarction;
- •Previously diagnosed heart failure;
- •Previously diagnosed atrial fibrillation;
- •Cardio-cerebral-kidney revascularization and/or other large arterial stent;
- •Currently on dialysis, or diagnosed with stage 4-5 chronic kidney disease, or eGFR <30 mL/ min/1.73m²;
- •Known to have congenital (such as aortic stenosis) or acquired organic heart disease;
- •Known to have any of the following severe diseases or conditions:
- •Digestive system: i. Previously diagnosed with any form of viral hepatitis that is currently still in the active phase; ii. Abnormal liver function test before enrollment (any of ALT, AST, GGT, TBIL, DBIL test 3 times higher than normal, or ALB≤30g/L); iii. Subtotal gastrectomy and/or gastrojejunostomy;
- •Respiratory system: previously diagnosed with pulmonary heart disease;
- •Presence of malignant tumors or other severe diseases;
- •Presence of long-term gastrointestinal symptoms such as ; anorexia, decreased appetite, nausea, and abdominal bloating;
- •Previously diagnosed with vitamin B12 deficiency and/or its related diseases.
- •Participant, at the investigator's discretion, is assessed to be unsuitable for the study, for reasons including but not limited to the presence of abnormal laboratory results, or clinical conditions;
- •Prior history of significant intolerance due to adverse reactions resulting from usage of amlodipine or other CCBs, valsartan or other ARBs, indapamide or other similar diuretics, metoprolol tartaric acid or other beta-blockers, or any drugs or health products containing folate or folic acid;
- •Regular consumption of folic acid or vitamin B compounds, or other compounds containing folic acid in the past 3 months;
- •The presence of any of the following conditions that could negatively influence a participant's ability to consent or participate in the trial:
- •Severe mental disorders;
- •Inability to express informed consent;
- •Unlikely to complete the study follow-up as specified by the protocol, or plans to relocate outside of the study area in the near future;
- •History of poor compliance when taking antihypertensive medications or is expected to have poor compliance during the study;
- •Refusal to participate, or inability to modify current drug regimen;
- •Women who are pregnant or breastfeeding; or subjects of childbearing potential who are unwilling or unable to use effective contraception during the study period.
- •Within one month prior to the first visit, having participated in any clinical trial for a drug that has not yet been officially approved by the state or is not currently approved for sale; or currently participating in any clinical trial that could potentially impact the results of this study (medication use, drug efficacy, drug interaction, etc.).
研究组 & 干预措施
Amlodipine (5mg/d)
Amlodipine 5mg x1 tablet + Amlodipine folic acid (dummy) x1 tablet + 5-MTHF (dummy) x2 tablets, taken orally, in the morning after waking up.
Amlodipine tablets, amlodipine folic acid placebos, and 5-MTHF placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine 5mg x2 tablets + amlodipine folic acid (dummy) x2 tablets + 5-MTHF (dummy) x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: Amlodipine besylate (Drug)
Amlodipine (5mg/d)
Amlodipine 5mg x1 tablet + Amlodipine folic acid (dummy) x1 tablet + 5-MTHF (dummy) x2 tablets, taken orally, in the morning after waking up.
Amlodipine tablets, amlodipine folic acid placebos, and 5-MTHF placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine 5mg x2 tablets + amlodipine folic acid (dummy) x2 tablets + 5-MTHF (dummy) x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: Amlodipine folic acid placebo (Drug)
Amlodipine (5mg/d)
Amlodipine 5mg x1 tablet + Amlodipine folic acid (dummy) x1 tablet + 5-MTHF (dummy) x2 tablets, taken orally, in the morning after waking up.
Amlodipine tablets, amlodipine folic acid placebos, and 5-MTHF placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine 5mg x2 tablets + amlodipine folic acid (dummy) x2 tablets + 5-MTHF (dummy) x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: 5-MTHF Placebos (Drug)
Amlodipine folic acid (5.8mg/d)
Amlodipine folic acid 5.8mg x1 tablet + amlodipine (dummy) x1 tablet + 5-MTHF (dummy) x2 tablets, taken orally, in the morning after waking up.
Amlodipine folic acid tablets, amlodipine placebos, and 5-MTHF placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine folic acid 5.8mg x2 tablets + amlodipine (dummy) x2 tablets + 5-MTHF (dummy) x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: Amlodipine besylate And Folic Acid (Drug)
Amlodipine folic acid (5.8mg/d)
Amlodipine folic acid 5.8mg x1 tablet + amlodipine (dummy) x1 tablet + 5-MTHF (dummy) x2 tablets, taken orally, in the morning after waking up.
Amlodipine folic acid tablets, amlodipine placebos, and 5-MTHF placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine folic acid 5.8mg x2 tablets + amlodipine (dummy) x2 tablets + 5-MTHF (dummy) x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: Amlodipine placebo (Drug)
Amlodipine folic acid (5.8mg/d)
Amlodipine folic acid 5.8mg x1 tablet + amlodipine (dummy) x1 tablet + 5-MTHF (dummy) x2 tablets, taken orally, in the morning after waking up.
Amlodipine folic acid tablets, amlodipine placebos, and 5-MTHF placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine folic acid 5.8mg x2 tablets + amlodipine (dummy) x2 tablets + 5-MTHF (dummy) x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: 5-MTHF Placebos (Drug)
Amlodipine folic acid (5.8mg/d) + 5-MTHF (0.4mg/d)
Amlodipine folic acid 5.8mg x1 tablet + 5-methyltetrahydrofolate 0.2mg x2 tablets + amlodipine (dummy) x1 tablet, taken orally, in the morning after waking up.
Amlodipine folic acid tablets, 5-MTHF, and amlodipine placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine folic acid 5.8mg x2 tablets + amlodipine (dummy) x2 tablets + 5-MTHF, 0.2mg x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: Amlodipine besylate And Folic Acid (Drug)
Amlodipine folic acid (5.8mg/d) + 5-MTHF (0.4mg/d)
Amlodipine folic acid 5.8mg x1 tablet + 5-methyltetrahydrofolate 0.2mg x2 tablets + amlodipine (dummy) x1 tablet, taken orally, in the morning after waking up.
Amlodipine folic acid tablets, 5-MTHF, and amlodipine placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine folic acid 5.8mg x2 tablets + amlodipine (dummy) x2 tablets + 5-MTHF, 0.2mg x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: 5-methyltetrahydrofolate (5-MTHF) (Drug)
Amlodipine folic acid (5.8mg/d) + 5-MTHF (0.4mg/d)
Amlodipine folic acid 5.8mg x1 tablet + 5-methyltetrahydrofolate 0.2mg x2 tablets + amlodipine (dummy) x1 tablet, taken orally, in the morning after waking up.
Amlodipine folic acid tablets, 5-MTHF, and amlodipine placebos are provided in aluminum-plastic blister plate. Each package includes 100 days of treatment drug (including 10 extra days of treatment for the follow-up window). A package of medication consists of 50 plates, each plate includes a total of 8 tablets arranged as follows: amlodipine folic acid 5.8mg x2 tablets + amlodipine (dummy) x2 tablets + 5-MTHF, 0.2mg x4 tablets. Affixed to the package is the randomized treatment drug label (400 tablets/package, 4 tablets/day).
干预措施: Amlodipine placebo (Drug)
结局指标
主要结局
First ischemic stroke
时间窗: By the end of the fifth year of the study
The primary aim of the trial is to determine whether amlodipine folic acid tablets (including Group B and Group C), compared to amlodipine alone (Group A), can further reduce the risk of first ischemic stroke among eligible participants with hypertension and the MTHFR 677 TT genotype.
次要结局
- First ischemic stroke (for refined treatment group comparisons)(By the end of the fifth year of the study)
- First stroke (ischemic and hemorrhagic)(By the end of the fifth year from baseline)
- Composite cardiovascular endpoint (first non-fatal stroke, first non-fatal myocardial infarction, cardiovascular death)(By the end of the fifth year from baseline)
- Kidney outcomes(By the end of the fifth year from baseline)
- First hemorrhagic stroke(By the end of the fifth year from baseline)
- First myocardial infarction(By the end of the fifth year from baseline)
- First coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI])(By the end of the fifth year from baseline)
- Cardiovascular death(By the end of the fifth year from baseline)