A Phase 4 interventional study of Amlodipine besylate and Amlodipine besylate And Folic Acid in Hypertension and MTHFR 677 TT Genotype, sponsored by Shenzhen Ausa Pharmed Co.,Ltd. Recruiting at 20 sites in China. Open to participants aged 45 Years to 74 Years. Per ClinicalTrials.gov, last updated 2025-02-26.
Sponsored by Shenzhen Ausa Pharmed Co.,Ltd · Phase 4, Interventional, and Treatment
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.
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)
The purpose of Run-in is to assess participants' compliance for following the amlodipine treatment regimen as well as to observe participants' tolerance to amlodipine, so as to screen out those with poor compliance or intolerance to amlodipine treatment.
The run-in phase lasted 2 to 4 weeks, during which oral administration of Amlodipine tablets (5 mg) was given once daily.
Period III: Randomized Treatment (V1-V21)
This is a 5-year period of randomized, double-blind, triple-dummy, controlled treatment. At each of the research centers, participants who remain eligible for participation in the study will be randomized into 3 treatment groups:
A. Amlodipine-only (5mg/d) with an amlodipine folic acid placebo and 5-MTHF placebos.
B. Amlodipine folic acid tablet (5.8mg/d) with amlodipine placebo and 5-MTHF placebo.
C. Amlodipine folic acid tablets (5.8mg/d) and 5-MTHF (0.4mg/d) with an amlodipine placebo in a 1:1:1 ratio, using the randomization and trial supply management (RTSM) platform.
During the treatment period, other antihypertensive drugs can be added to achieve blood pressure control (BP ≤140/90mmHg), including Valsartan (80mg/d), or/and Indapamide (1.5mg/d), or/and metoprolol tartrate tablets (25mg/d). Participants will be followed up every 3 months during the treatment period, and the treatment drugs will be distributed at each visit.
A total of 24,000 participants will be randomly assigned to one of three treatment groups (Group A n=8,000, Group B n=8,000, Group C n=8,000). Based on published data from CSPPT (Huo et al, JAMA, 2015), the 5-year cumulative incidence of first ischemic stroke in the amlodipine-only group is 3.5%. Assuming the 5-year cumulative incidence of first ischemic stroke in the amlodipine-only group is around 3.5%, this trial has 80% power to detect a 20% difference between group A and group B+C in the observed hazard ratio (HR) for incident ischemic stroke (HR≤0.80), at a two-sided significance level of α=0.05. If instead, the 5-year incidence of ischemic stroke in the amlodipine-only group is 2.5%, this trial has 80% power to detect a 23% difference between the treatment groups (A vs B+C) (HR≤0.77).
There are two planned interim analyses, one at the end of the third year, and another at the end of the fourth year. The O'Brien-Fleming alpha-spending function will be used to define the significance level of each interim analysis to ensure that the final overall two-sided significance level of α=0.05 is met.
6,114 studies on the registry are indexed under Hypertension; 912 are open to participants now.
This study's planned enrollment of 24,000 is above the median of 100 across 4,575 interventional studies indexed under Hypertension.
Browse Hypertension studies →Shenzhen Ausa Pharmed Co.,Ltd is the lead sponsor of 7 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Randomized-treatment phase inclusion criteria:
Exclusion Criteria:
Known to have any of the following severe diseases or conditions:
The presence of any of the following conditions that could negatively influence a participant's ability to consent or participate in the trial:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Drug: Amlodipine besylate · Drug: Amlodipine folic acid placebo · Drug: 5-MTHF Placebos
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).
Drug: Amlodipine besylate And Folic Acid · Drug: Amlodipine placebo · Drug: 5-MTHF Placebos
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).
Drug: Amlodipine besylate And Folic Acid · Drug: 5-methyltetrahydrofolate (5-MTHF) · Drug: Amlodipine placebo
The amlodipine used in this study is a listed product.
Also known as: Amlodipine
Drug pages: Amlodipine · Folic Acid
The amlodipine besylate and folic acid tablets have been approved for listing by the China Food and Drug Administration, approval number: Zhunzi H20180020.
Also known as: Amlodipine Folic Acid, Anye
The 5-MTHF used in this study is a listed product.
Also known as: 5-MTHF
Amlodipine placebos are dummy pills of amlodipine with identical appearance.
Also known as: Amlodipine (dummy)
Amlodipine folic acid placebos are dummy pills of amlodipine folic acid with identical appearance.
Also known as: Amlodipine folic acid (dummy)
5-MTHF placebos are the dummy pills of 5-MTHF with identical appearance.
Also known as: 5-MTHF (dummy)
First ischemic stroke
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.
Time frame: By the end of the fifth year of the study
First ischemic stroke (for refined treatment group comparisons)
We will examine whether there exist significant differences in efficacy in reducing the risk of first ischemic stroke between the following pairs of treatment groups: Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: By the end of the fifth year of the study
First stroke (ischemic and hemorrhagic)
We will examine whether there exist significant differences in efficacy in reducing the risk of first stroke between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: By the end of the fifth year from baseline
Composite cardiovascular endpoint (first non-fatal stroke, first non-fatal myocardial infarction, cardiovascular death)
We will examine whether there exist significant differences in efficacy in reducing the risk of composite cardiovascular endpoint between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: By the end of the fifth year from baseline
Kidney outcomes
1. The primary kidney outcome is composite kidney outcome, defined as: (1) a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73 m2 if the baseline eGFR is 60 mL/min/1.73 m2 or more, or (2) a decrease in eGFR of 50% or more if the baseline eGFR is less than 60 mL/min/1.73 m2, or (3) end-stage kidney disease (ESKD) (eGFR \<15 mL/min/1.73m2 or dialysis or kidney transplantation). 2. Secondary kidney outcomes: (1) eGFR decline ≥40% from baseline, or end-stage kidney disease; (2) annual rate of relative decline in eGFR; (3) Incidence of proteinuria, or progression of proteinuria. We will examine whether there exist significant differences in treatment efficacy on the above kidney endpoints between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: By the end of the fifth year from baseline
First hemorrhagic stroke
We will examine whether amlodipine folic acid tablets (including Groups B and C), compared to amlodipine alone (Group A), show significantly greater efficacy in preventing first hemorrhagic stroke.
Time frame: By the end of the fifth year from baseline
First myocardial infarction
We will examine whether amlodipine folic acid tablets (including Groups B and C), compared to amlodipine alone (Group A), show significantly greater efficacy in preventing first myocardial infarction.
Time frame: By the end of the fifth year from baseline
First coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI])
We will examine whether amlodipine folic acid tablets (including Groups B and C), compared to amlodipine alone (Group A), show significantly greater efficacy in preventing first coronary revascularization.
Time frame: By the end of the fifth year from baseline
Cardiovascular death
We will examine whether amlodipine folic acid tablets (including Groups B and C), compared to amlodipine alone (Group A), show significantly greater efficacy in preventing cardiovascular death.
Time frame: By the end of the fifth year from baseline
Malignant tumors
We will examine whether there exist significant differences in efficacy in reducing the risk of malignant tumors between the Groups B + C and Group A.
Time frame: By the end of the fifth year of the study
All-cause mortality
We will examine whether there exist significant differences in efficacy in reducing the risk of all-cause mortality between the Groups B + C and Group A.
Time frame: By the end of the fifth year of the study
Blood pressure levels
We will examine whether there exist significant differences in treatment efficacy on the blood pressure levels between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: 1) Blood pressure levels at one year, three-year and at the end of follow-up(up to 5 years). 2) Average blood pressure levels across all visits in the first and third years of follow-up, as well as for the entire follow-up period (up to 5 years).
Blood pressure variability
We will examine whether there exist significant differences in treatment efficacy on the blood pressure variability between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: 1) Average blood pressure variability across all visits in the first and third years of follow-up, and across all visits throughout the entire follow-up period (up to 5 years).
Blood pressure target achievement rates
We will examine whether there exist significant differences in treatment efficacy on the blood pressure target achievement rates between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: 1) Blood pressure target achievementrates at 1-year, 3-year and at the end of follow-up(up to 5 years). 2) Average bloodpressure target achievement rates across all visits in the first and third years of follow-up, and for the entire follow-up period.]
Serum folate level
We will examine whether there exist significant differences in treatment efficacy on the serum folate levels between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: Serum folate levels at one year, three-year and at the end of follow-up(up to 5 years).
Serum folate change
We will examine whether there exist significant differences in treatment efficacy on the serum folate changes between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: Serum folate changes at one year, three-year and at the end of follow-up(up to 5 years).
Plasma tHcy level
We will examine whether there exist significant differences in treatment efficacy on the plasma total homocysteine levels between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: Plasma total homocysteine levels at one year, three-year and at the end of follow-up(up to 5 years).
Plasma tHcy change
We will examine whether there exist significant differences in treatment efficacy on the plasma total homocysteine changes between the following pairs of treatment groups: Groups B + C vs. Group A Group B vs. Group A Group C vs. Group A Group B vs. Group C
Time frame: Plasma total homocysteine changes at one year, three-year and at the end of follow-up(up to 5 years).
Plan to share: No
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Studies of the drugs tested here: Amlodipine · Folic Acid
Shenzhen Ausa Pharmed Co.,Ltd