China Stroke Primary Prevention Trial for Subjects With Hypertension and MTHFR 677 TT Genotype (CSPPT2-TT) — CSPPT2-TT  

Hypertension Clinical Trial

Official title: Comparative Efficacy of Amlodipine Folic Acid vs. Amlodipine on the Risk of First Ischemic Stroke Among Patients With Hypertension and MTHFR 677 TT Genotype: A Multi-center, Randomized, Controlled Clinical Trial

Status Not yet recruiting

Clinical Trial Summary

This is a multicenter, randomized, controlled clinical trial. It aims to investigate the treatment effects of amlodipine folic acid, and its combination of 5-methyltetrahydrofolate (5-MTHF), compared to amlodipine, on reducing the risk of first ischemic stroke among those participants with the MTHFR 677 TT genotype and hypertension.

This study consists of 3 phases: Screening, Run-in period (0 or 2 weeks), and randomized treatment (5 years), with a prospective, randomized, open-label, blinded end-point design.

Clinical Trial Description

This study consists of 3 phases: Screening, Run-in period, Randomized treatment.

Phase I: Screening (V0)

The purpose of phase I is to obtain informed consent and make a preliminary assessment of the patient.

At the first screening visit (V0), or prior to the official treatment visit, a clinical examination will be performed to determine the patient's clinical diagnosis and to determine eligibility for inclusion in the study. General demographic information will be obtained and questions related to the inclusion/exclusion criteria of this study will be asked. Additionally, this will be the time to discuss the impact of participant vacation/travel plans on adherence and compliance with the trial protocol.

Phase II: Run-in Period (VD)

Eligible patients who have not used antihypertensive drugs of Dihydropyridine Calcium Channel Blockers (CCBs) in the past two months, or who require further observation such as patients taking dihydropyridine CCBs but under the circumstances that may affect the evaluation of compliance and safety to patients like taking medicine irregularly, self-medication, and poor blood pressure control, will begin the treatment of amlodipine (5mg/d) for a 2-week run-in period. Those patients who have been taking antihypertensive drugs of dihydropyridine CCBs in the past two months and who report no adverse reactions, will skip the run-in period and directly begin the randomized treatment phase.

The primary purpose of this phase is to assess participant compliance for following the amlodipine treatment regimen as well as to observe the participant's tolerance to amlodipine, so as to avoid admitting those participants with poor compliance or an intolerance to amlodipine, into the randomized treatment phase.

Phase III: Randomized Treatment (V1-V21)

The third phase consists of a 5-year period of randomized treatment. Patients who remain eligible for participation in the study will be randomized into 3 treatment groups: either amlodipine only tablets (5mg/d), or amlodipine folic acid tablets (5.8mg/d), or amlodipine folic acid tablets (5.8mg/d) + 5-MTHF (0.4mg/d). During the 5-year randomized treatment period, other antihypertensive drugs can be combined with the treatment drug to achieve blood pressure control, including Candesartan (8mg/d) or/and Indapamide (1.5mg/d). Patients will be followed-up every 3 months during the treatment period, and the treatment drug will be distributed at each visit. During this period, participants should continue to avoid taking medications that may interfere with the evaluation of treatment efficacy.

After the Run-in Period, eligible participants, stratified by research centers, were randomly assigned, in a 1:1 ratio, to receive the two study treatments. Randomization was performed centrally by means of a computer-generated random-number sequence.

This study plans to enroll 24,000 participants. Based on the results of previous studies, the annual incidence of first ischemic stroke in people with hypertension and the MTHFR TT genotype without folic acid supplementation is 0.64%. Assuming that the 5-year incidence of first ischemic stroke in the amlodipine group is greater than 2.5%, this study could observe a relative risk difference of more than 25% between the groups with over 80% power at a two-sided significance level of α=0.05. For an assumed annual incidence of first ischemic stroke greater than 3.5%, a relative risk difference of over 20% between the groups could be observed with 80% or more power.

For every 200 confirmed primary outcome events, an interim analysis will be conducted. This study anticipates conducting 4 interim analyses. 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 will be α=0.05. ;

Related Conditions & MeSH terms

• Hypertension

• NCT number: NCT04974151
• Study type: Interventional
• Source: Shenzhen Ausa Pharmed Co.,Ltd
• Contact: Minqing Tian, PhD
• Phone: 86-18818680849
• Email: tianminqing@163.com
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 1, 2022
• Completion date: April 30, 2027