CSPPT- Chronic Kidney Diseases Study (CSPPT-CKD)

Enalapril Maleate and Folic Acid Tablets for Prevention of Chronic Kidney Diseases in Patients With Hypertension: a 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 renal function decline among the patients with primary hypertension when compared to enalapril maleate.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension; Hyperhomocysteinemia
• Intervention / Treatment: Drug: Enalapril maleate; Drug: Enalapril maleate and folic acid tablets

Detailed Description

Elevated blood concentration of homocysteine (Hcy) has been suggested as a modifiable, independent risk factor for coronary artery disease, stroke, and deep vein thrombosis. Prevalence of hyperhomocysteinemia and folic acid deficiency in China are significantly higher than those in Europe and USA. The investigators' preliminary research demonstrated that blood concentration of Hcy was negatively correlated to estimated glomerular filtration rate (eGFR), a key index of kidney function. However, the question as to whether Hcy-lowering therapy with folic acid can reduce the risk of chronic kidney disease(CKD) remains to be answered.

This study, exploiting the hypertensive population of CSPPT trial (ClinicalTrials.gov register number: NCT00794885), is intended to compare the effects of enalapril maleate and folic acid tablets versus enalapril maleate in preventing renal function decline among the patients with primary hypertension. The results from this trial may have the potential to transform current clinical and public health findings into practice in the prevention of chronic kidney disease(CKD) in China.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Anhui
    • Anqing, Anhui, China, 246000
      • Anqing Branch, Anhui Institute of Biomedical Research
  • Jiangsu
    • Lianyungang, Jiangsu, China, 222003
      • Lianyungang Center for Advanced Research in Cardiovascular Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 methylenetetrahydrofolate reductase (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);
• Having a 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Enalapril maleate and folic acid tablets; A fixed combination drug is given. The dose is fixed in enalapril 10 mg / folic acid 0.8 mg per day.	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.
ACTIVE_COMPARATOR: Enalapril maleate; Enalapril maleate 10 mg per day is given	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function decline	Renal function decline was defined based on one of more of the following : (1) A certain drop in eGFR, was defined as a drop in GFR category (≥90[G1], 60-89[G2], 45-59[G3a], 30-44[G3b], 15-29[G4], <15[G5] ml/min/1.73m2) accompanied by a 25% or greater drop in eGFR from baseline; (2) Rapid progression, was defined as a sustained decline in eGFR of more than 5 ml/min/1.73m2/yr.	Serum creatinine was examined at baseline and at the final visit (5 years) of the trial.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average decline rate in eGFR (ml/min/1.73m2/yr).		Serum creatinine was examined at baseline and at the final visit (5 years) of the trial.
New-onset chronic kidney disease based on eGFR（eGFR<60 ml/min/1.73 m2）		Serum creatinine was examined at baseline and at the final visit (5 years) of the trial.
New-onset albuminuria		Albuminuria was examined at baseline and at the final visit (5 years) of the trial.
A composite of renal events.	The composite endpoint is consisted of: 1)End stage renal disease (ESRD);2)Doubling of serum creatinine; and 3)Renal disease-induced death.	Every 3 months during the trial, up to 5 years

Collaborators and Investigators

• Sponsor: Shenzhen Ausa Pharmed Co.,Ltd
• Collaborators: Nanfang Hospital of Southern Medical University
• Investigators: Principal Investigator: Fanfan Hou, MD, Division of Nephrology, Nanfang Hospital, Southern Medical University; Principal Investigator: Xin Xu, MD, Guangdong Provincial Institute of Nephrology

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ANTICIPATED): August 1, 2014

Study Registration Dates

• First Submitted: May 29, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (ESTIMATE): June 7, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 18, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Hypertension; Randomized controlled trial; Folic acid; Chronic kidney disease; Hyperhomocysteinemia; MTHFR C677T genotype; Renal function decline
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Nutrition Disorders; Genetic Diseases, Inborn; Avitaminosis; Deficiency Diseases; Malnutrition; Metabolism, Inborn Errors; Malabsorption Syndromes; Amino Acid Metabolism, Inborn Errors; Vitamin B Deficiency; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Hyperhomocysteinemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Angiotensin-Converting Enzyme Inhibitors; Maleic acid; Enalaprilat; Enalapril; Folic Acid
• Other Study ID Numbers: Ausa-CSPPT-CKD