Preventing strokes in people with hypertension and a specific genetic makeup

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

This study is testing if different combinations of a blood pressure medication and vitamins can help prevent strokes in people with high blood pressure who have a specific genetic makeup.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 24000 (estimated)
• Ages: 45 Years to 74 Years
• Sex: All
• Sponsor: Shenzhen Ausa Pharmed Co.,Ltd (Industry-sponsored)
• Locations: 20 sites (Bengbu, Anhui and 19 other locations)
• Trial ID: NCT04974151 on ClinicalTrials.gov

What this trial studies

This clinical trial is a multi-center, randomized, double-blind, triple-dummy controlled trial involving 24,000 Chinese men and women diagnosed with hypertension and possessing the MTHFR 677 TT genotype. Participants will be randomly assigned to one of three treatment groups: one receiving amlodipine alone, another receiving amlodipine with folic acid, and a third receiving amlodipine with both folic acid and 5-methyltetrahydrofolate. The primary goal is to assess the effectiveness of these treatments in preventing the first occurrence of ischemic stroke over a five-year period. The study includes a screening phase to ensure eligibility and a run-in phase to evaluate compliance and tolerance to the treatment regimen.

Who should consider this trial

Good fit: Ideal candidates for this study are men and women aged 45 to 75 with a diagnosis of hypertension and the MTHFR 677 TT genotype.

Not a fit: Patients who do not have hypertension or the MTHFR 677 TT genotype may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce the incidence of ischemic strokes in patients with hypertension and the MTHFR 677 TT genotype.

How similar studies have performed: Other studies have shown promising results with similar approaches in managing hypertension and stroke prevention, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Men and women, aged ≥45 and \<75 years.
2. Hypertension: Previously diagnosed with primary hypertension and has been taking antihypertensive medication within the past two weeks; OR has not been taking antihypertensive medications within the last two weeks, but meets the following criteria for hypertension: SBP≥140 mmHg and/or DBP≥90 mmHg (average of at least 2 measurements each time) at two separate (not on the same day) clinical visits.
3. MTHFR 677 TT genotype (based on the test results from the central laboratory during the screening period or a previous official test report from a laboratory with medical testing qualifications).
4. Voluntarily participates and has given signed informed consent.

Randomized-treatment phase inclusion criteria:

1. Good compliance during the run-in period, and unlikely to discontinue treatment;
2. No stroke or cardiovascular events during the run-in period;
3. The participant voluntarily agrees to continue the study.

Exclusion Criteria:

1. Previously diagnosed secondary hypertension;
2. Previously diagnosed stroke;
3. Previously diagnosed myocardial infarction;
4. Previously diagnosed heart failure;
5. Previously diagnosed atrial fibrillation;
6. Cardio-cerebral-kidney revascularization and/or other large arterial stent;
7. Currently on dialysis, or diagnosed with stage 4-5 chronic kidney disease, or eGFR \<30 mL/ min/1.73m²;
8. Known to have congenital (such as aortic stenosis) or acquired organic heart disease;
9. Known to have any of the following severe diseases or conditions:

   1. Digestive system: i. Previously diagnosed with any form of viral hepatitis that is currently still in the active phase; ii. Abnormal liver function test before enrollment (any of ALT, AST, GGT, TBIL, DBIL test 3 times higher than normal, or ALB≤30g/L); iii. Subtotal gastrectomy and/or gastrojejunostomy;
   2. Respiratory system: previously diagnosed with pulmonary heart disease;
   3. Presence of malignant tumors or other severe diseases;
   4. Presence of long-term gastrointestinal symptoms such as ; anorexia, decreased appetite, nausea, and abdominal bloating;
   5. Previously diagnosed with vitamin B12 deficiency and/or its related diseases.
10. Participant, at the investigator's discretion, is assessed to be unsuitable for the study, for reasons including but not limited to the presence of abnormal laboratory results, or clinical conditions;
11. Prior history of significant intolerance due to adverse reactions resulting from usage of amlodipine or other CCBs, valsartan or other ARBs, indapamide or other similar diuretics, metoprolol tartaric acid or other beta-blockers, or any drugs or health products containing folate or folic acid;
12. Regular consumption of folic acid or vitamin B compounds, or other compounds containing folic acid in the past 3 months;
13. The presence of any of the following conditions that could negatively influence a participant's ability to consent or participate in the trial:

    1. Dementia;
    2. Severe mental disorders;
    3. Inability to express informed consent;
    4. Unlikely to complete the study follow-up as specified by the protocol, or plans to relocate outside of the study area in the near future;
    5. History of poor compliance when taking antihypertensive medications or is expected to have poor compliance during the study;
14. Refusal to participate, or inability to modify current drug regimen;
15. Women who are pregnant or breastfeeding; or subjects of childbearing potential who are unwilling or unable to use effective contraception during the study period.
16. Within one month prior to the first visit, having participated in any clinical trial for a drug that has not yet been officially approved by the state or is not currently approved for sale; or currently participating in any clinical trial that could potentially impact the results of this study (medication use, drug efficacy, drug interaction, etc.).

Where this trial is running

Bengbu, Anhui and 19 other locations

• First Affillated Hospital of Bengbu Medical University — Bengbu, Anhui, China (Not_yet_recruiting)
• Bozhou People's Hospital — Bozhou, Anhui, China (Not_yet_recruiting)
• Chizhou People's Hospital — Chizhou, Anhui, China (Not_yet_recruiting)
• Taihe County People's Hospital — Fuyang, Anhui, China (Not_yet_recruiting)
• Peking University First Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Yangjiang People's Hospital — Yangjiang, Guangdong, China (Not_yet_recruiting)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (Not_yet_recruiting)
• The First Affiliated Hospital of Hunan University of Medicine — Huaihua, Hunan, China (Not_yet_recruiting)
• Loudi Central Hospital — Loudi, Hunan, China (Not_yet_recruiting)
• Lianyungang Oriental Hospital — Lianyungang, Jiangsu, China (Recruiting)
• The First People's Hospital of Lianyungang — Lianyungang, Jiangsu, China (Not_yet_recruiting)
• The Second People's Hospital of Lianyungang — Lianyungang, Jiangsu, China (Not_yet_recruiting)
• Yancheng First People's Hospital — Yancheng, Jiangsu, China (Not_yet_recruiting)
• The First Affiliated Hospital of Gannan Medical University — Ganzhou, Jiangxi, China (Not_yet_recruiting)
• Second Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Weinan Central Hospital — Weinan, Shaanxi, China (Not_yet_recruiting)
• Tengzhou Central People's Hospital — Zaozhuang, Shandong, China (Not_yet_recruiting)
• Chengdu Fifth People's Hospital — Chengdu, Sichuan, China (Not_yet_recruiting)
• Deyang People's Hospital — Deyang, Sichuan, China (Not_yet_recruiting)
• The Affiliated Hospital of Southwest Medical University — Luzhou, Sichuan, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Jianping Li, MD, PhD — Peking University First Hospital
• Study coordinator: Minqing Tian, PhD

Conditions Hypertension; MTHFR 677 TT Genotype; Folic acid; Homocysteine; MTHFR 677 TT genotype; Randomized controlled trial; Ischemic stroke; 5-MTHF