Preventing strokes in people with specific hypertension and genetic factors

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

This study is testing if adding folic acid to amlodipine can help prevent strokes in Chinese adults aged 45 to 75 with certain high blood pressure and genetic factors.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 32000 (estimated)
• Ages: 45 Years to 74 Years
• Sex: All
• Sponsor: Shenzhen Ausa Pharmed Co.,Ltd (industry)
• Locations: 20 sites (Bengbu, Anhui and 19 other locations)
• Trial ID: NCT04974138 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of a combination treatment of amlodipine and folic acid compared to amlodipine alone in preventing ischemic strokes among Chinese adults aged 45 to 75 with H-type hypertension and specific MTHFR 677 genotypes. The study will involve 32,000 participants who will be randomized into two groups, with one receiving amlodipine and the other receiving a combination of amlodipine and folic acid over a five-year period. Participants will undergo a screening and run-in phase to ensure compliance and tolerance to the treatment before entering the randomized treatment phase.

Who should consider this trial

Good fit: Ideal candidates for this study are Chinese men and women aged 45 to 75 with H-type hypertension and MTHFR 677 CC or CT genotype.

Not a fit: Patients who do not have H-type hypertension or the specified MTHFR 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 H-type hypertension and specific genetic predispositions.

How similar studies have performed: Previous studies have shown promising results in managing hypertension and stroke prevention with similar approaches, but this specific combination is being tested for the first time.

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 CC or CT 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. Plasma total homocysteine ≥10 µmol/L;
5. Serum folate level \<12 ng/mL;
6. Has voluntarily agreed to participate and provided 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 Affiliated Hospital of Bengbu Medical University — Bengbu, Anhui, China (NOT_YET_RECRUITING)
• Bozhou — 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: Yong Huo, MD, PhD — Peking University First Hospital
• Study coordinator: Minqing Tian, PhD

Conditions: Hypertension, MTHFR 677 CC or CT Genotype, Elevated Plasma Homocysteine, Insufficient Plasma Folate Levels, Folic acid, Homocysteine, MTHFR C677T genotype, Randomized controlled trial