Cerebral Small Vessel DiseasesPhase 4FAITHNCT05169021
Folic Acid and Intensive Antihypertensive Therapy for Hypertension With CSVD
A Phase 4 study testing Amlodipine folic acid 5.8mg+intensive antihypertensive therapy, Amlodipine folic acid 5.8mg+standard antihypertensive therapy and Amlodipine+intensive antihypertensive therapy in people with Cerebral Small Vessel Diseases and Stroke, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
The primary objectives of this trial are: 1. 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… Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Cerebral Small Vessel Diseases, Stroke
- What is being tested?
- Amlodipine folic acid 5.8mg+intensive antihypertensive therapy, Amlodipine folic acid 5.8mg+standard antihypertensive therapy and Amlodipine+intensive antihypertensive therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15,000 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2021to 31 Dec 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 35-75 years;
- Meets any of the following criteria:
- 1) 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).
- 3. 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. 4. mRS score ≤2; 5. Serum Hcy ≥10 µmol/L or MTHFR 677 TT genotype; 6. Signed informed consent form.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Tiantan Hospital
Beijing, Beijing Municipality, 100070
Jinglin Mo, +86 18801125231, mojinglin_dmu@163.com
About this study
Official title: 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
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.
- 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.
Read the detailed description
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.
- Conditions
- Cerebral Small Vessel Diseases, Stroke
- Being tested
- Amlodipine folic acid 5.8mg+intensive antihypertensive therapy, Amlodipine folic acid 5.8mg+standard antihypertensive therapy, Amlodipine+intensive antihypertensive therapy, Amlodipine+standard antihypertensive therapy
- Keywords
- Cerebral Small Vessel Diseases, Stroke recurrence, Hypertension, Homocysteine, Folic acid
- Medical subject headings
- Cerebral Small Vessel Diseases, Stroke, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amlodipine folic acid 5.8mg+intensive antihypertensive therapyDrug
Amlodipine folic acid tablet 5.8mg, taken daily, in the morning after waking.
To achieve target blood pressure(SBP<130mmHg), this study will provide, if needed, concurrent antihypertensive medications. Patients will be asked to discontinue all prior concurrent medications. Recommended treatment options are described below:
- Add candesartan 4mg;
- Add indapamide 2.5mg;
- Increase dose of candesartan to 8mg;
- Increase dose of amlodipine to 7.5mg-10mg.
Amlodipine folic acid 5.8mg+standard antihypertensive therapyDrug
Amlodipine folic acid tablet 5.8mg, taken daily, in the morning after waking.
To achieve target blood pressure (SBP:130-140mmHg), this study will provide, if needed, concurrent antihypertensive medications. Patients will be asked to discontinue all prior concurrent medications. Recommended treatment options are described below:
- Add candesartan 4mg;
- Add indapamide 2.5mg;
- Increase dose of candesartan to 8mg;
- Increase dose of amlodipine to 7.5mg-10mg.
Amlodipine+intensive antihypertensive therapyDrug
Amlodipine tablet 5.8mg, taken daily, in the morning after waking.
To achieve target blood pressure (SBP: 130-140 mmHg), this study will provide, if needed, concurrent antihypertensive medications. Patients will be asked to discontinue all prior concurrent medications. Recommended treatment options are described below:
- Add candesartan 4mg;
- Add indapamide 2.5mg;
- Increase dose of candesartan to 8mg;
- Increase dose of amlodipine to 7.5mg-10mg.
Amlodipine+standard antihypertensive therapyDrug
Also called Standard antihypertensive therapy
Amlodipine tablet 5.8mg, taken daily, in the morning after waking.
To achieve target blood pressure (SBP: 130-140 mmHg), this study will provide, if needed, concurrent antihypertensive medications. Patients will be asked to discontinue all prior concurrent medications. Recommended treatment options are described below:
- Add candesartan 4mg;
- Add indapamide 2.5mg;
- Increase dose of candesartan to 8mg;
- Increase dose of amlodipine to 7.5mg-10mg.
| Study group | Role | What they receive |
|---|---|---|
| Amlodipine folic acid 5.8mg+intensive antihypertensive therapy | Active comparator | This group will receive intensive antihypertensive therapy (systolic blood pressure(SBP) <130 mmHg); with amlodipine folic acid 5.8mg. Receives: Drug: Amlodipine folic acid 5.8mg+intensive antihypertensive therapy |
| Amlodipine folic acid 5.8mg+standard antihypertensive therapy | Active comparator | This group will receive standard antihypertensive therapy (SBP: 130-140 mmHg); with amlodipine folic acid 5.8mg. Receives: Drug: Amlodipine folic acid 5.8mg+standard antihypertensive therapy |
| Amlodipine+intensive antihypertensive therapy | Active comparator | This group will receive intensive antihypertensive therapy (systolic blood pressure(SBP) <130 mmHg); with amlodipine 5.0mg. Receives: Drug: Amlodipine+intensive antihypertensive therapy |
| Amlodipine+standard antihypertensive therapy | Placebo comparator | This group will receive standard antihypertensive therapy (SBP: 130-140 mmHg); with amlodipine 5.0mg. Receives: Drug: Amlodipine+standard antihypertensive therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause stroke (including fatal and non-fatal stroke)
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
Measured: 4 year after randomization
Combined cardio-cerebrovascular events
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.
Measured: 4 year after randomization
Secondary outcomes (8)
Combined cardio-cerebrovascular events
Secondary outcome for assessing 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 combined cardio-cerebrovascular events in cerebral small vascular disease (CSVD) patients with hypertension and elevated homocysteine (Hcy) level.
Measured: 4 year after randomization
All-cause stroke (including fatal and non-fatal stroke)
Secondary outcome for assessing the effect of intensive antihypertensive therapy (SBP<130 mmHg) versus standard antihypertensive therapy (SBP 130-<140 mmHg) in reducing risk of stroke occurrence in CSVD patients with hypertension and elevated Hcy level.
Measured: 4 year after randomization
Ischemic stroke
Percentage of patients within follow-up period new ischemic stroke events.
Measured: 4 year after randomization
Hemorrhagic stroke
Percentage of patients within follow-up period new hemorrhagic stroke events.
Measured: 4 year after randomization
Myocardial infarction
Percentage of patients within follow-up period new myocardial infarction events.
Measured: 4 year after randomization
Hospitalization from heart failure
Hospitalization, or an emergency department visit requiring treatment with infusion therapy, for a clinical syndrome that presents with multiple signs and symptoms consistent with cardiac decompensation/ inadequate cardiac pump function within follow-up period.
Measured: 4 year after randomization
Cardio-cerebrovascular death
Cardio-cerebrovascular death includes death caused by acute myocardial infarction (MI), sudden cardiac death, death caused by heart failure (HF), death caused by stroke, death caused by cardiovascular surgery, death caused by cardiovascular hemorrhage and other cardiovascular causes.
Measured: 4 year after randomization
All-cause death
This is death due to various causes, including cardiovascular and non-vascular deaths and deaths from unknown causes.
Measured: 4 year after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2021
- Study start31 Dec 2021 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cerebral Small Vessel DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongjun Wang, Beijing Tiantan Hospital
- Investigators
- Yongjun Wang, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05169021
- Sponsor's protocol ID
- FAITH
- Acronym
- FAITH
- Status last verified
- Dec 2021
- First submitted
- 10 Dec 2021
- Last updated
- 23 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Wang J, Yang X, Yang T, Xiao C, Zhao G, Dong Q, Zhu D, Wang X, Ge J, Zhao L, Hu D, Liu L, Hou FF; CSPPT Investigators. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015 Apr 7;313(13):1325-35. doi: 10.1001/jama.2015.2274.
PubMed 25771069Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004 Feb 4;291(5):565-75. doi: 10.1001/jama.291.5.565.
PubMed 14762035VITATOPS Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 2010 Sep;9(9):855-65. doi: 10.1016/S1474-4422(10)70187-3. Epub 2010 Aug 3.
PubMed 20688574SPS3 Study Group; Benavente OR, Coffey CS, Conwit R, Hart RG, McClure LA, Pearce LA, Pergola PE, Szychowski JM. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013 Aug 10;382(9891):507-15. doi: 10.1016/S0140-6736(13)60852-1. Epub 2013 May 29.
PubMed 23726159Croall ID, Tozer DJ, Moynihan B, Khan U, O'Brien JT, Morris RG, Cambridge VC, Barrick TR, Blamire AM, Ford GA, Markus HS; PRESERVE Study Team. Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease: The PRESERVE Randomized Clinical Trial. JAMA Neurol. 2018 Jun 1;75(6):720-727. doi: 10.1001/jamaneurol.2017.5153.
PubMed 29507944