NCT00794885

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20,702

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started May 2008

Longer than P75 for phase_4

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2008

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

November 19, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 20, 2008

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

August 12, 2014

Status Verified

August 1, 2014

Enrollment Period

5.3 years

First QC Date

November 19, 2008

Last Update Submit

August 11, 2014

Conditions

Primary Hypertension

Keywords

hypertensionstrokecardiovascular eventsenalaprilfolic acidrandomized controlled trialMTHFR C677T genotype

Outcome Measures

Primary Outcomes (1)

  • First attack of symptomatic stroke ( ischemic or hemorrhagic)

    Patients are followed-up every 3 months. All endpoint outcomes are assessed by the Endpoint Adjudication Committee of the study.

    during the trial period

Secondary Outcomes (5)

  • Composite major cardiovascular events

    during the trial period

  • All-cause death

    during the trial period

  • First attack of ischemic stroke and resultant death

    during the trial period

  • First attack of hemorrhagic stroke and resultant death

    during the trial period

  • Myocardial infarction and resultant death

    during the trial period

Other Outcomes (1)

  • Malignant tumors

    during the trial period

Study Arms (2)

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.

Drug: Enalapril/folic acid

Enalapril

ACTIVE COMPARATOR

Enalapril maleate 10 mg per day is given

Drug: Enalapril maleate

Interventions

Enalapril/folic acidDRUG

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.

Also known as: Enalapril Maleate and Folic Acid Tablet
Enalapril/folic acid
Enalapril maleateDRUG

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

Also known as: Lameiya,Yabao Pharmaceutical
Enalapril

Eligibility Criteria

Age45 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Anqing Branch, Anhui Institute of Biomedical Research

Anqing, Anhui, 246000, China

Location

Lianyungang Center for Advanced Research in Cardiovascular Diseases

Lianyungang, Jiangsu, 222003, China

Location

Related Publications (38)

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    PMID: 15947278BACKGROUND

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    PMID: 39821957DERIVED

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  • Lei W, Liu Z, Su Z, Meng P, Zhou C, Chen X, Hu Z, Xiao A, Zhou M, Huang L, Zhang Y, Qin X, Wang J, Zhu F, Nie J. Hyperhomocysteinemia potentiates megakaryocyte differentiation and thrombopoiesis via GH-PI3K-Akt axis. J Hematol Oncol. 2023 Jul 27;16(1):84. doi: 10.1186/s13045-023-01481-x.

    PMID: 37501059DERIVED

  • Li Y, Song Y, Liu L, Wang X, Zhou Z, Zhang N, Wang Z, Chen P, Shi H, Huo Y, Xu X, Li J. Inverse Association Between Baseline Plasma Selenium Concentrations and Risks of Renal Function Decline in Hypertensive Adults. J Nutr. 2023 Jan 14;152(12):2754-2760. doi: 10.1093/jn/nxac211.

    PMID: 36083982DERIVED

  • He Q, Zhang N, Liang Q, Wang Z, Chen P, Song Y, Zhou Z, Wei Y, Duan Y, Wang B, Qin P, Qin X, Xu X. Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT). Front Nutr. 2022 Jul 12;9:946277. doi: 10.3389/fnut.2022.946277. eCollection 2022.

    PMID: 35903445DERIVED

  • Wei Y, Wang Z, He Q, Siddiqi SM, Zhou Z, Liu L, Song Y, Chen P, Li J, Zhang Y, Mao G, Wang B, Tang G, Qin X, Xu X, Huo Y, Guo H, Zhang H. Inverse Association between Plasma Phylloquinone and Risk of Ischemic Stroke in Chinese Adults with Hypertension and High BMI: A Nested Case-Control Study. J Nutr. 2022 Aug 9;152(8):1927-1935. doi: 10.1093/jn/nxac131.

    PMID: 35660920DERIVED

  • Song M, Xu BP, Liang Q, Wei Y, Song Y, Chen P, Zhou Z, Zhang N, He Q, Liu L, Liu T, Zhang K, Hu C, Wang B, Xu X, Shi H. Association of serum choline levels and all-cause mortality risk in adults with hypertension: a nested case-control study. Nutr Metab (Lond). 2021 Dec 20;18(1):108. doi: 10.1186/s12986-021-00637-1.

    PMID: 34930356DERIVED

  • Song Y, Li J, Liu L, Xu R, Zhou Z, Xu B, Lin T, Chen P, Li H, Li Y, Liu C, Huang X, Wang B, Zhang Y, Li J, Huo Y, Ren F, Xu X, Zhang H, Qin X. Plasma Vitamin E and the Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study. Front Nutr. 2021 Nov 3;8:734580. doi: 10.3389/fnut.2021.734580. eCollection 2021.

    PMID: 34805240DERIVED

  • Wei Y, Xu B, Wang Z, Zhou Z, Liu L, Lin T, Song Y, Li J, Zhang Y, Huo Y, Mao G, Wang B, Tang G, Qin X, Zhang H, Wang X, Guo H, Xu X. Joint Associations between Plasma 25-Hydroxyvitamin D, Glycemic Status, and First Stroke in General Hypertensive Adults: Results from the China Stroke Primary Prevention Trial (CSPPT). J Nutr. 2022 Jan 11;152(1):246-254. doi: 10.1093/jn/nxab339.

    PMID: 34558624DERIVED

  • Wang Z, Ma H, Song Y, Lin T, Liu L, Zhou Z, Wei Y, Huang X, Chen P, Liu C, Li Y, Wang B, Li J, Zhang Y, Huo Y, Zhang H, Xu X, Qin X, Guo H. Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial. Am J Clin Nutr. 2022 Jan 11;115(1):222-231. doi: 10.1093/ajcn/nqab320.

    PMID: 34549258DERIVED

  • Zhang Y, Zhou C, Li J, Zhang Y, Xie D, Liang M, Wang B, Song Y, Wang X, Huo Y, Hou FF, Xu X, Qin X. Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults. Cardiovasc Diabetol. 2020 Oct 24;19(1):186. doi: 10.1186/s12933-020-01161-x.

    PMID: 33099298DERIVED

  • Xie L, Zhao BX, Luo J, Li Y, Zhu F, Li GF, He M, Wang B, Zhang H, Cai Y, Huo Y, Wang X, Hou FF, Xu X, Qin X, Nie J. A U-shaped association between serum betaine and incident risk of first ischemic stroke in hypertensive patients. Clin Nutr. 2020 Aug;39(8):2517-2524. doi: 10.1016/j.clnu.2019.11.011. Epub 2019 Nov 15.

    PMID: 31806397DERIVED

  • Zhang Y, He P, Li Y, Zhang Y, Li J, Liang M, Wang G, Tang G, Song Y, Wang B, Liu C, Liu L, Cui Y, Wang X, Huo Y, Xu X, Qin X. Positive association between baseline brachial-ankle pulse wave velocity and the risk of new-onset diabetes in hypertensive patients. Cardiovasc Diabetol. 2019 Aug 28;18(1):111. doi: 10.1186/s12933-019-0915-0.

    PMID: 31462258DERIVED

  • Zhang J, Cao J, Zhang Y, Li H, Zhang H, Huo Y, Li J, Liu X, Wang X, Qin X, Xu X. Baseline Plasma Zinc and Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study. Stroke. 2019 Nov;50(11):3255-3258. doi: 10.1161/STROKEAHA.119.027003. Epub 2019 Aug 26.

    PMID: 31446884DERIVED

  • Zhang J, Cao J, Zhang H, Jiang C, Lin T, Zhou Z, Song Y, Li Y, Liu C, Liu L, Wang B, Tang G, Li J, Zhang Y, Cui Y, Huo Y, Yang Y, Ling W, Yang J, Guo H, Wang X, Xu X, Qin X. Plasma copper and the risk of first stroke in hypertensive patients: a nested case-control study. Am J Clin Nutr. 2019 Jul 1;110(1):212-220. doi: 10.1093/ajcn/nqz099.

    PMID: 31161196DERIVED

  • Wang J, Guo H, Lin T, Song Y, Zhang H, Wang B, Zhang Y, Li J, Huo Y, Wang X, Qin X, Xu X. A Nested Case-Control Study on Plasma Vitamin E and Risk of Cancer: Evidence of Effect Modification by Selenium. J Acad Nutr Diet. 2019 May;119(5):769-781. doi: 10.1016/j.jand.2018.11.017. Epub 2019 Jan 31.

    PMID: 30713028DERIVED

  • Yu Y, Zhang H, Song Y, Lin T, Zhou Z, Guo H, Liu L, Wang B, Liu C, Li J, Zhang Y, Huo Y, Wang C, Wang X, Hou FF, Qin X, Xu X. Plasma retinol and the risk of first stroke in hypertensive adults: a nested case-control study. Am J Clin Nutr. 2019 Feb 1;109(2):449-456. doi: 10.1093/ajcn/nqy320.

    PMID: 30624586DERIVED

  • Yang X, Zhang M, Song R, Liu C, Huo Y, Qian G. The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT. Cardiovasc Ther. 2018 Dec;36(6):e12473. doi: 10.1111/1755-5922.12473. Epub 2018 Nov 20.

    PMID: 30372582DERIVED

  • Nie J, Xie L, Zhao BX, Li Y, Qiu B, Zhu F, Li GF, He M, Wang Y, Wang B, Liu S, Zhang H, Guo H, Cai Y, Huo Y, Hou FF, Xu X, Qin X. Serum Trimethylamine N-Oxide Concentration Is Positively Associated With First Stroke in Hypertensive Patients. Stroke. 2018 Sep;49(9):2021-2028. doi: 10.1161/STROKEAHA.118.021997.

    PMID: 30354996DERIVED

  • Kong X, Huang X, Zhao M, Xu B, Xu R, Song Y, Yu Y, Yang W, Zhang J, Liu L, Zhang Y, Tang G, Wang B, Hou FF, Li P, Cheng X, Zhao S, Wang X, Qin X, Li J, Huo Y. Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke. J Am Coll Cardiol. 2018 May 15;71(19):2136-2146. doi: 10.1016/j.jacc.2018.02.072.

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  • Huang X, Li Y, Li P, Li J, Bao H, Zhang Y, Wang B, Sun N, Wang J, He M, Yin D, Tang G, Chen Y, Cui Y, Huang Y, Hou FF, Qin X, Huo Y, Cheng X. Association between percent decline in serum total homocysteine and risk of first stroke. Neurology. 2017 Nov 14;89(20):2101-2107. doi: 10.1212/WNL.0000000000004648. Epub 2017 Oct 13.

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  • Li Y, Liang M, Wang G, Wang B, He M, Tang G, Yin D, Xu X, Huo Y, Cui Y, Hou FF, Qin X. Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients: A Post Hoc Analysis of the Renal Substudy of CSPPT (China Stroke Primary Prevention Trial). Hypertension. 2017 Aug;70(2):300-306. doi: 10.1161/HYPERTENSIONAHA.117.09404. Epub 2017 Jun 12.

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  • Wei R, Liu LS, Wang LW, Li YB, Zhang T, Liu J, Zuo SW, Jia SH, Song YX, Wu ZY, Duan C, Ge YY, Li HB, Xiong J, Jia X, Wang X, Kong W, Xu XP, Guo W, Huo Y. Association of Resting Heart Rate with Infrarenal Aortic Diameter: A Cross Sectional Study in Chinese Hypertensive Adults. Eur J Vasc Endovasc Surg. 2015 Dec;50(6):714-21. doi: 10.1016/j.ejvs.2015.05.022. Epub 2015 Oct 21.

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  • Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Wang J, Yang X, Yang T, Xiao C, Zhao G, Dong Q, Zhu D, Wang X, Ge J, Zhao L, Hu D, Liu L, Hou FF; CSPPT Investigators. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015 Apr 7;313(13):1325-35. doi: 10.1001/jama.2015.2274.

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  • Wang Y, Li X, Qin X, Cai Y, He M, Sun L, Li J, Zhang Y, Tang G, Wang B, Sun N, Xu X, Liu L, Xu X, Huo Y. Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45-75 years. Br J Nutr. 2013 Apr 14;109(7):1284-93. doi: 10.1017/S0007114512003157. Epub 2012 Jul 31.

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MeSH Terms

Conditions

Essential HypertensionHypertensionStroke

Interventions

EnalaprilFolic Acid

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

DipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and ProteinsPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Yong Huo, M.D.

    The First Hospital, Beijing University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 19, 2008

First Posted

November 20, 2008

Study Start

May 1, 2008

Primary Completion

August 1, 2013

Study Completion

June 1, 2014

Last Updated

August 12, 2014

Record last verified: 2014-08

Locations

CN(2)