Title

China Stroke Primary Prevention Trial
Enalapril Maleate and Folic Acid Tablets for Primary Prevention of Stroke in Patients With Hypertension: a Post-marketing, Double-blind, Randomized Controlled Trial.
  • Phase

    Phase 4
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Study Participants

    20702
The purpose of this trial is to confirm that enalapril maleate and folic acid tablets is more effective in preventing stroke among the patients with primary hypertension when compared to enalapril maleate.
Primary hypertension is the most important risk factor leading to cardiovascular events. Successful management of hypertension is a key to prevent these events. Hyperhomocysteinemia (HHcy) is another independent risk factor, especially for stroke. Our team's prospective nested case-control study of 39165 subjects in China showed that incidence of cardiovascular events (especially stroke) was strongly associated with plasma level of total homocysteine (tHcy). The coexistence of hypertension and HHcy dramatically increased the risk of stroke by 25 to 30 times as compared to the subjects without the two risk factors (Graham et al, 1997). Findings from previous and our studies clearly indicate that simultaneous control of hypertension and HHcy is pivotal in reducing cardiovascular events morbidity and mortality in China.

It has been well documented that folic acid is effective in lowering the level of plasma tHcy. While controversial remains on its efficacy on preventing cardiovascular events, a study done by our team: "Efficacy of folic acid supplementation in stroke prevention: a meta-analysis" (Wang et al, 2007) provide coherent evidence that folic acid supplementation can decrease the risk of stroke by 18%, and 25% in populations where folic fortification was not issued, or used for primary prevention.

C677T gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) is one of the genetic determinators of plasma tHcy level. Observational studies showed that individuals with TT genotype tend to have high plasma tHcy and elevated risk of cardiovascular events (Cronin et al. 2005), and folic acid supplementation led to a remarkable reduction in plasma tHcy. In short, previous studies by others and by our team have provided strong rationale for our proposed trial as detailed below.

The hypothesis of the current study is that a combination of antihypertensive drug (e.g., enalapril) with folic acid is not only efficacious, but also is safe and highly cost-effective than antihypertensive (e.g., enalapril) used alone to prevent stroke in hypertensive patients.

This trial will enroll 20,000 patients with primary hypertension and with known MTHFR C677T genotype. Subjects will be first stratified by genotypes, and then randomly assigned to treatment groups. The study patients will be instructed to take orally enalapril 10 mg daily or enalapril/folic acid 10mg/0.8mg tablets daily for a maximum of 5 years. The follow-up is given every 3 months.

The incidence and time of first-time stroke episode (primary endpoint) or composite cardiovascular events are used as endpoints. They will be compared by treatment groups with and without stratification by C677T gene polymorphisms. The potential interaction between treatment groups and C677T gene polymorphisms on therapeutic efficacy will also be tested.

This will be the first and largest trial of this kind in Chinese population. The findings from this trial may have the potential to transform current clinical and public health findings into practice.
Study Started
May 31
2008
Primary Completion
Aug 31
2013
Study Completion
Jun 30
2014
Last Update
Aug 12
2014
Estimate

Drug Enalapril/folic acid

Enalapril/folic acid, (10mg enalapril/0.8mg folic acid)/tablet, taken orally and once daily for a maximum of 5 years. Combination with other anti-hypertension drugs are allowed.

  • Other names: Enalapril Maleate and Folic Acid Tablet

Drug Enalapril maleate

Enalapril, 10mg/tablet, taken orally once daily for a maximum of 5 consecutive years. Combination with other anti-hypertension drugs are allowed.

  • Other names: Lameiya,Yabao Pharmaceutical

Enalapril/folic acid Experimental

A fixed combination drug is given. The dose is fixed in enalapril 10 mg / folic acid 0.8 mg per day.

Enalapril Active Comparator

Enalapril maleate 10 mg per day is given

Criteria

Inclusion Criteria:

BP≥140/90 mmHg in both of the two screening visits or currently under anti-hypertension treatment
45 - 75 years old
Successful determination of MTHFR C677T genotype
For pre-menopausal women, agreed to use contraceptives during the trial
Signed the written informed consent

Exclusion Criteria:

Having a history of stroke
Having a history of myocardial infarction
Having a history of physician diagnosed heart failure
Post- coronary revascularization
Severe somatic disease such as cancer
Secondary hypertension
Congenital or acquired organic heart diseases
Contraindicated to angiotensin-converting enzyme inhibitor(ACEI)
History of ACEI adverse effects
Currently long-term use of folic acid or vitamin B12 or vitamin B6
Pregnant or child breastfeeding women
Severe mental disorders
Lab tests indicating abnormal liver or kidney function
Unwilling to participate the trial, unwilling to change the current antihypertensive treatment
No Results Posted