China Stroke Primary Prevention Trial
Condition: Primary Hypertension
MeSH terms: Hypertension; Essential Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Enalapril/folic acid; Enalapril maleate
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Enalapril, 10mg/tablet, taken orally once daily for a maximum of 5 consecutive years. Combination with other anti-hypertension drugs are allowed.
Other intervention name(s): Enalapril Maleate and Folic Acid Tablet; Lameiya,Yabao Pharmaceutical
Intervention MeSH terms: Folic Acid; Vitamin B Complex; Enalapril; Enalaprilat; Maleic acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: hypertension; stroke; cardiovascular events; enalapril; folic acid; randomized controlled trial; MTHFR C677T genotype