Folic Acid and Intensive Antihypertensive Therapy for Hypertension With CSVD

NCT05169021 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: FAITH
• Study Type: interventional
• Target: 15,000
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this trial are:

1. 1.Efficacy evaluation of amlodipine folic acid tablets:
2. 2.Intensive Antihypertensive Therapy:

Conditions

Cerebral Small Vessel Diseases; Stroke

Keywords

Cerebral Small Vessel Diseases; Stroke recurrence; Hypertension; Homocysteine; Folic acid

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  4 year after randomization

Secondary Outcomes (8)

• Combined cardio-cerebrovascular events

  4 year after randomization

• All-cause stroke (including fatal and non-fatal stroke)

  4 year after randomization

• Ischemic stroke

  4 year after randomization

• Hemorrhagic stroke

  4 year after randomization

• Myocardial infarction

  4 year after randomization

Other Outcomes (6)

• Malignant tumors occurence

  4 year after randomization

• Changes in total image load score of CSVD

  4 year after randomization

• Changes in WMLs and brain volume

  4 year after randomization

Study Arms (4)

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.

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.

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.

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.

Drug: Amlodipine+standard antihypertensive therapy

Interventions

Amlodipine folic acid 5.8mg+intensive antihypertensive therapy DRUG

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: 1. Add candesartan 4mg; 2. Add indapamide 2.5mg; 3. Increase dose of candesartan to 8mg; 4. Increase dose of amlodipine to 7.5mg-10mg.

Amlodipine folic acid 5.8mg+intensive antihypertensive therapy

Amlodipine folic acid 5.8mg+standard antihypertensive therapy DRUG

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: 1. Add candesartan 4mg; 2. Add indapamide 2.5mg; 3. Increase dose of candesartan to 8mg; 4. Increase dose of amlodipine to 7.5mg-10mg.

Amlodipine folic acid 5.8mg+standard antihypertensive therapy

Amlodipine+intensive antihypertensive therapy DRUG

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: 1. Add candesartan 4mg; 2. Add indapamide 2.5mg; 3. Increase dose of candesartan to 8mg; 4. Increase dose of amlodipine to 7.5mg-10mg.

Amlodipine+intensive antihypertensive therapy

Amlodipine+standard antihypertensive therapy DRUG

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: 1. Add candesartan 4mg; 2. Add indapamide 2.5mg; 3. Increase dose of candesartan to 8mg; 4. Increase dose of amlodipine to 7.5mg-10mg.

Also known as: Standard antihypertensive therapy

Amlodipine+standard antihypertensive therapy

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. 4. mRS score ≤2; 5. Serum Hcy ≥10 µmol/L or MTHFR 677 TT genotype; 6. Signed informed consent form.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100070, China

Location

Related Publications (5)

• 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.

  PMID: 25771069 RESULT

• Toole 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.

  PMID: 14762035 RESULT

• VITATOPS 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.

  PMID: 20688574 RESULT

• SPS3 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.

  PMID: 23726159 RESULT

• Croall 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.

  PMID: 29507944 RESULT

MeSH Terms

Conditions

Cerebral Small Vessel Diseases; Stroke; Hypertension

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Yongjun Wang

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinglin Mo

CONTACT

+86 18801125231; mojinglin_dmu@163.com

Anxin Wang

CONTACT

0086-010-59978350; anxin0907@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Beijing Tiantan Hospital, Capital Medical University

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: December 23, 2021
• Study Start: December 31, 2021
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)