Folic Acid and Intensive Antihypertensive Therapy for Cerebrovascular and Cardiovascular Events Prevention Among Patients With Hypertension and Cerebral Small Vascular Diseases (FAITH)----A Multicenter, Randomized, Controlled, Open-label, 2x2 Factorial, Blinded End-point Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15,000
- 试验地点
- 1
- 主要终点
- Combined cardio-cerebrovascular events
研究概览
简要总结
The primary objectives of this trial are:
- Efficacy evaluation of amlodipine folic acid tablets:
To assess the effects of amlodipine folic acid tablets 5.8 mg (5 mg amlodipine + 0.8 mg folic acid)versus amlodipine tablets 5 mg in preventing all-cause stroke in cerebral small vascular disease (CSVD) patients with hypertension and elevated homocysteine (Hcy) level. 2. Intensive Antihypertensive Therapy:
To assess the effect of intensive antihypertensive therapy (SBP<130 mmHg) versus standard antihypertensive therapy (SBP 130-<140 mmHg) in reducing risk of combined cardio-cerebrovascular events in CSVD patients with hypertension and elevated Hcy level, using two basic anti-hypertensive drugs, amlodipine tablets 5 mg or amlodipine folic acid tablets 5.8 mg.
详细描述
Hypertension is highly prevalent risk factor for stroke, particularly for stroke associated with CSVD. Blood pressure (BP) lowering has been considered an important measure for preventing stroke and progression of CSVD. Moreover, uncertainty remains regarding the efficacy of folic acid therapy for secondary prevention of stroke because of limited and inconsistent data. We propose to conduct a randomized, double-blind, placebo-controlled, multicenter, 2×2 factorial designed clinical trial to test the primary hypothesis that 1) whether amlodipine folic acid is more effective than amlodipine in reducing the risk of all-cause stroke (including fatal and non-fatal stroke) over a follow-up period among patients with CSVD. 2) whether an intensive treatment strategy (a systolic BP target of <130mmHg) is more effective than a standard treatment strategy (a systolic BP target of 130-140mmHg) in reducing the risk of combined cardio-cerebrovascular events.
Both Intention-to-treat Analysis (ITT) and Per-protocol set (PPS) were used for analysis.
We will use Kaplan-Meier estimates of the cumulative risk of stroke (ischemic or hemorrhagic) event and combined cardio-cerebrovascular events during follow-up period, with hazards ratios and 95% CI calculated using Cox proportional hazards methods and the log-rank test to evaluate the treatment effect. All statistics will be 2-sided with P<0.05 considered significant, accounting for interim analyses.
All patients who received study drugs and with at least one safety follow-up record will be included in the safety population. The data for safety evaluation included adverse reactions observed during the trial and changes in laboratory data before and after treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 35-75 years;
- •Meets any of the following criteria:
- •Lacunar infarction occurring within the period of seven days up to one year post-infarction, diagnosed by head MRI/CT (meeting modified Fisher criteria*); 2）Head MRI indicating white matter hyperintensity, 4≥Fazekas score*≥2; 3）Head MRI indicating white matter hyperintensity, Fazekas=1, combined with old subcortical vascular lacunar infarction;
- •For modified Fisher criteria and Fazekas score, see FAITH main study appendix 1 and appendix 6).
- •Medical recorded history of hypertension. Systolic blood pressure SBP: 130-180 mm Hg on 0 or 1 medication SBP: 130-170 mm Hg on up to 2 medications SBP: 130-160 mm Hg on up to 3 medications.
- •mRS score ≤2;
- •Serum Hcy ≥10 µmol/L or MTHFR 677 TT genotype;
- •Signed informed consent form.
排除标准
- •Patients with secondary hypertension;
- •Symptomatic intracranial and extracranial artery stenosis (stenosis ≥50%), or asymptomatic intracranial and extracranial artery stenosis (stenosis≥70%);
- •Patients who have undergone revascularization of the heart, brain, or kidney, or other aortic stenting procedures;
- •Any symptoms of orthostatic hypotension when measuring standing blood pressure, or if standing SBP <110mmHg;
- •Bilateral renal artery stenosis;
- •Patients who have previously taken candesartan or other angiotensin receptor antagonist (ARB) type medication, indapamide or other similar diuretic type medication, or any medication or health product containing folic acid, and reported adverse reactions;
- •Patients who have indicators for specific antihypertensive medications (e.g. β-blockers after acute myocardial infarction, RAS blockers for prevention of cardiovascular disease, α-blockers for treatment of benign prostate hyperplasia);
- •Within the last three months, regular usage of vitamin supplements containing folic acid, B6, or B12, or usage of folic acid antagonists (e.g. methotrexate);
- •Patients undergoing dialysis or with stage 4-5 chronic kidney disease, or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m²;
- •History of epilepsy or currently using anti-epileptic medication;
- •Pregnant and lactating women, or women planning to become pregnant;
- •Life expectancy less than four years;
- •Within the last month, participation in another clinical trial;
- •Any patient determined by the researchers to be unsuitable for the present study.
研究组 & 干预措施
Amlodipine folic acid 5.8mg+intensive antihypertensive therapy
This group will receive intensive antihypertensive therapy (systolic blood pressure(SBP) <130 mmHg); with amlodipine folic acid 5.8mg.
干预措施: Amlodipine folic acid 5.8mg+intensive antihypertensive therapy (Drug)
Amlodipine folic acid 5.8mg+standard antihypertensive therapy
This group will receive standard antihypertensive therapy (SBP: 130-140 mmHg); with amlodipine folic acid 5.8mg.
干预措施: Amlodipine folic acid 5.8mg+standard antihypertensive therapy (Drug)
Amlodipine+intensive antihypertensive therapy
This group will receive intensive antihypertensive therapy (systolic blood pressure(SBP) <130 mmHg); with amlodipine 5.0mg.
干预措施: Amlodipine+intensive antihypertensive therapy (Drug)
Amlodipine+standard antihypertensive therapy
This group will receive standard antihypertensive therapy (SBP: 130-140 mmHg); with amlodipine 5.0mg.
干预措施: Amlodipine+standard antihypertensive therapy (Drug)
结局指标
主要结局
Combined cardio-cerebrovascular events
时间窗: 4 year after randomization
This aims to assess the effect of intensive antihypertensive therapy (SBP\<130 mmHg) versus standard antihypertensive therapy (SBP 130-\<140 mmHg) in reducing risk of combined cardio-cerebrovascular events in CSVD patients with hypertension and elevated Hcy level.
All-cause stroke (including fatal and non-fatal stroke)
时间窗: 4 year after randomization
This aims to assess the effects of amlodipine folic acid tablets 5.8 mg (5 mg amlodipine + 0.8 mg folic acid)versus amlodipine tablets 5 mg in preventing stroke occurrence in cerebral small vascular disease (CSVD) patients with hypertension and elevated homocysteine (Hcy) level
次要结局
- All-cause stroke (including fatal and non-fatal stroke)(4 year after randomization)
- Myocardial infarction(4 year after randomization)
- Cardio-cerebrovascular death(4 year after randomization)
- All-cause death(4 year after randomization)
- Ischemic stroke(4 year after randomization)
- Hemorrhagic stroke(4 year after randomization)
- Combined cardio-cerebrovascular events(4 year after randomization)
- Hospitalization from heart failure(4 year after randomization)
研究者
Yongjun Wang
President of Beijing Tiantan Hospital, Capital Medical University
Beijing Tiantan Hospital