China Stroke Primary Prevention Trial (CSPPT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Anhui Medical University
Information provided by (Responsible Party):
Shenzhen Ausa Pharmed Co.,Ltd
ClinicalTrials.gov Identifier:
NCT00794885
First received: November 19, 2008
Last updated: June 9, 2012
Last verified: June 2012

November 19, 2008
June 9, 2012
May 2008
August 2014   (final data collection date for primary outcome measure)
First attack of symptomatic stroke ( ischemic or hemorrhagic) [ Time Frame: during the trial period ] [ Designated as safety issue: No ]
Patients are followed-up every 3 months. All endpoint outcomes are assessed by the Endpoint Judicatory Board of the study.
First attack of symptomatic stroke ( ischemic or hemorrhagic) [ Time Frame: At the end of 2nd or 4th years of the trial ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00794885 on ClinicalTrials.gov Archive Site
  • Composite major cardiovascular events [ Time Frame: during the trial period ] [ Designated as safety issue: No ]
  • All-cause death [ Time Frame: during the trial period ] [ Designated as safety issue: Yes ]
  • First attack of ischemic stroke and resultant death [ Time Frame: during the trial period ] [ Designated as safety issue: No ]
  • First attack of hemorrhagic stroke and resultant death [ Time Frame: during the trial period ] [ Designated as safety issue: No ]
  • Myocardial infarction and resultant death [ Time Frame: during the trial period ] [ Designated as safety issue: No ]
  • Specific and composite cardiovascular events and resulting death [ Time Frame: At the end of 2nd or 4th years of the trial ] [ Designated as safety issue: No ]
  • All-cause death [ Time Frame: At the end of 2nd or 4th years of the trial ] [ Designated as safety issue: No ]
  • First attack of ischemic stroke and resulting death [ Time Frame: At the end of 2nd or 4th years of the trial ] [ Designated as safety issue: No ]
  • First attack of hemorrhagic stroke and resulting death [ Time Frame: At the end of 2nd or 4th years of the trial ] [ Designated as safety issue: No ]
  • Myocardial infarction and resulting death [ Time Frame: At the end of 2nd or 4th years of the trial ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

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 15,000 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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Primary Hypertension
  • Drug: Enalapril maleate and folic acid tablets
    Enalapril maleate and folic acid tablets, (10mg/0.8mg)/tablet, taken orally and once daily for a maximum of 5 years. Combination with other anti-hypertension drugs are allowed.
  • 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 Name: Lameiya(Yabao Pharmaceutical)
  • Experimental: Enalapril/folic acid
    A fixed combination drug is given. The dose is fixed in enalapril 10 mg / folic acid 0.8 mg per day.
    Intervention: Drug: Enalapril maleate and folic acid tablets
  • Active Comparator: Enalapril
    Enalapril maleate 10 mg per day is given
    Intervention: Drug: Enalapril maleate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20702
August 2014
August 2014   (final data collection date for primary outcome measure)

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 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
Both
45 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
China
 
NCT00794885
Ausa-CSPPT
Yes
Shenzhen Ausa Pharmed Co.,Ltd
Shenzhen Ausa Pharmed Co.,Ltd
Anhui Medical University
Principal Investigator: Yong Huo, M.D. The First Hospital, Beijing University
Shenzhen Ausa Pharmed Co.,Ltd
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP