CSPPT- Chronic Kidney Diseases Study (CSPPT-CKD)

• ClinicalTrials.gov Identifier: NCT01871740
• Recruitment Status: Withdrawn
• First Posted: June 7, 2013
• Last Update Posted: January 20, 2016
• Sponsor: Shenzhen Ausa Pharmed Co.,Ltd
• Collaborator: Nanfang Hospital of Southern Medical University
• Information provided by (Responsible Party): Shenzhen Ausa Pharmed Co.,Ltd

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypertension; Hyperhomocysteinemia	Drug: Enalapril maleate and folic acid tablets; Drug: Enalapril maleate	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Enalapril Maleate and Folic Acid Tablets for Prevention of Chronic Kidney Diseases in Patients With Hypertension: a Double-blind Randomized Controlled Trial
• Study Start Date: May 2008
• Actual Primary Completion Date: June 2014
• Estimated Study Completion Date: August 2014

Arms and Interventions

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 Name: Lameiya(Yabao Pharmaceutical)

Outcome Measures

Primary Outcome Measures :

1. Renal function decline [ Time Frame: Serum creatinine was examined at baseline and at the final visit (5 years) of the trial. ]

   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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.

Contacts and Locations

Locations

China, Anhui

Anqing Branch, Anhui Institute of Biomedical Research

Anqing, Anhui, China, 246000

China, Jiangsu

Lianyungang Center for Advanced Research in Cardiovascular Diseases

Lianyungang, Jiangsu, China, 222003

Sponsors and Collaborators

Shenzhen Ausa Pharmed Co.,Ltd

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

More Information

• Responsible Party: Shenzhen Ausa Pharmed Co.,Ltd
• ClinicalTrials.gov Identifier: NCT01871740
• Other Study ID Numbers: Ausa-CSPPT-CKD
• First Posted: June 7, 2013
• Last Update Posted: January 20, 2016
• Last Verified: January 2016

Keywords provided by Shenzhen Ausa Pharmed Co.,Ltd:

Folic acid; Renal function decline; Hypertension; Hyperhomocysteinemia; Chronic kidney disease; MTHFR C677T genotype; Randomized controlled trial

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Hypertension; Hyperhomocysteinemia; Vascular Diseases; Cardiovascular Diseases; Urologic Diseases; Renal Insufficiency; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Malabsorption Syndromes; Metabolic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Folic Acid; Enalapril; Enalaprilat; Maleic acid; Hematinics; Vitamin B Complex; Vitamins; Micronutrients; Physiological Effects of Drugs; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Angiotensin-Converting Enzyme Inhibitors