The Relationship Between HHcy and Contrast-induced Nephropathy in Hypertensive Patients After Coronary Artery Diagnosis and Treatment (CONTRAST-CADT)

Department of Geriatrics

Contrast-induced nephropathy has become the third-largest cause of hospital acquired acute renal injury, and which morbidity is only less than that of renal hypoperfusion and renal toxicity of drugs, about 11%of all cases. Pathophysiologic mechanisms of contrast-induced nephropathy(CIN) is not entirely clear yet. May be associated with renal hemodynamic changes, medullary ischemia because of renal blood flow reduction, oxidative stress, endothelial dysfunction ,contrast agents damage the epithelium of renal tubular directly and so on. Currently the studies have proved that inflammation(CRP, TNF-α and NF-қB) played a role in CIN.It is well-know that the hyperhomocysteinemia(HHCY) is a independent risk factor for cardiovascular diseases, which has pro-inflammatory effects. Researches showed that Hcy stimulated CRP generation by the NMDAr-ROS-ERK1 / 2 / p38-NF-қB signaling pathway and triggered inflammatory response. We will compare the CIN incidence of different plasma Hcy levels in adults hypertensive patients undergoing coronary artery diagnosis and treatment(CAG and PCI). CIN was defined as an absolute ≥0.5mg/dl or a relative ≥25% increase in the serum creatinine level at 48 hours after the procedure. The relationship between decreased plasma Hcy levels and blood pressure values by using Enalapril Maleate and Folic Acid Tablets(as the program-based antihypertension) and recovery of CIN has been observed. Using univariate and multivariate Logistic regression to analyse the relationship between HHcy and CIN, and taking receiver operating characteristic (ROC) curve to select the best Hcy plasma levels that which can predict the CIN and the probability. This study will help us to understand the relationship between HHcy and CIN that course of the procedure in adults hypertensive patients, preoperative plasma Hcy levels can predict the incidence of CIN and whether Enalapril Maleate Folic Acid tablets can reduce the CIN of hypertensive patients with HHcy. Which has important clinical significance. This study also offer feasibility for further research that HHcy plays a role in pathogenesis and specific signaling pathways of CIN.

Study Overview

• Status: Completed
• Conditions: Coronary Disease; Hypertension; Nephropathy; Contrast Media; Homocysteine; Angioplasty,Balloon,Coronary
• Intervention / Treatment: Drug: Placebo; Drug: Enalapril Maleate Tablets(as the program-based antihypertension); Drug: Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension)

Detailed Description

The first stage: the establishment of hypothesis of the relationship between HHcy and CIN The demographic and laboratory data were retrieved from the His system. Hypertensive patients who underwent coronary artery diagnosis and treatment(CAG or PCI) at Fuling Central Hospital of Chongqing City from June 2013 to August 2015 were initially included in the present study. The baseline characteristics of the hypertensive patients according to the tertile of plasma homocysteine level will be analysed, and investigating the incidence of CIN and relevant factors.

The second stage: To verify the hypothesis of relationship between HHcy and CIN in patients with hypertension CER research method

1. patients who accepted the coronary artery diagnosis and treatment(CAG and PCI ) in departments of Geriatrics and Cardiovascular within one year were initially participate in. According to the statistics that we finished, the proportion of hypertension in the total patients who underwent procedure has reached about 80%, so there has more than 4000 patients with hypertension within 1 year will be involved. The levels of plasma Hcy in the total patients will be detected. The patients will divided into 2 groups according to the plasma Hcy levels,The hypertensive patients(adults) with their plasma Hcy levels ≥10 umol/L will take Enalapril Maleate and Folic Acid Tablets(as the program-based antihypertension), The hypertensive patients(adults) with their plasma Hcy levels <10 umol/L will take Enalapril Maleate Tablets(as the program-based antihypertension).The procedure will be carried out after blood pressure valves within normal range.
2. All patients will be followed up for 3 months, they will return to hospital 3 times(once a month) after discharged. Urine routine and renal function will be tested, to register blood pressure,any change of body condition and other related factors per months, and plasma Hcy levels will be detected in the hypertensive patients with higher-homocysteinemia at second and third months after discharged.
3. Data collection and data statistics will be carried out per 2 months. All patients who undergoing coronary artery diagnosis and treatment(CAG and PCI)will be divided into group A without hypertension, group B that the hypertensive patients with their plasma Hcy levels <10 umol/L and group C that the hypertensive patients with plasma Hcy levels ≥10 umol/L. To compare CIN incidence of the 3 groups at each time point, the CIN incidence of group B and group C will be compared, and association between CIN and the levels of blood pressure and plasma Hcy will be analyzed by multivariate logistic regression analysis according to the ROC curve.

• Study Type: Interventional
• Enrollment (Actual): 4000
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Fuling, Chongqing, China, 408099
      • TIAN Jie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

From November 2015 to April 2017 , all consecutive patients admitted to the participating centers for the patients who undergoing coronary artery diagnosis and treatment(CAG or PCI) will been considered eligible，about 5500 cases.

Exclusion Criteria:

• Who requires long-term peritoneal or hemodialysis.
• Who had been underwent a kidney transplantation.
• Renal failure with a creatinine level >3 mg/dl.
• Who had been received the contrast agent within 2 weeks or had been received metformin, aminoglycoside antibiotics or acetylcysteine within 48 hours.
• Iodine allergy, acute and chronic infections and hyperthyroidism.
• Left ventricular ejection fraction <30%.
• Secondary hypertension.
• Who can not be tolerated ACEI.
• Any other surgical contraindications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A, without hypertension; The patients who will not be taken the drugs of antihypertension and antihomocysteine.	Drug: Placebo
Experimental: Group B, hypertension; The hypertensive patients with their plasma Hcy levels <10 umol/L will be taken the drugs of antihypertension(Enalapril Maleate Tablets,as the program-based antihypertension)	Drug: Enalapril Maleate Tablets(as the program-based antihypertension)
Experimental: Group C,hypertension and hyperhomocysteinemia; The hypertensive patients with their plasma Hcy levels ≥10 umol/L will be taken the drugs of antihypertension and antihomocysteine( Enalapril Maleate and Folic Acid Tablets,as the program-based antihypertension)	Drug: Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of contrast-induced nephropathy	CIN was defined as an absolute ≥0.5mg/dl or a relative ≥25% increase in the serum creatinine level at 48 hours after the procedure.	At 48 hours after the procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dialysis	The hypertensive patients in the 3 groups who had been diagnosed as CIN need to dialysis.	Within the first 3 months after procedure.
Ischemic stroke	The hypertensive patients in the 3 groups who had been diagnosed of ischemic stroke (focal neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT or MRI	Within the first 3 months after procedure.
All cause mortality	Any cause of death in patients	Within the first 3 months after procedure.

Collaborators and Investigators

• Sponsor: Fuling Central Hospital of Chongqing City

Publications and helpful links

General Publications

• Kim SJ, Choi D, Ko YG, Kim JS, Han SH, Kim BK, Kang SW, Hong MK, Jang Y, Choi KH, Yoo TH. Relation of homocysteinemia to contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2011 Oct 15;108(8):1086-91. doi: 10.1016/j.amjcard.2011.06.010. Epub 2011 Jul 24.
• Bolognese L, Falsini G, Grotti S, Limbruno U, Liistro F, Carrera A, Angioli P, Picchi A, Ducci K, Pierli C. The contrast media and nephrotoxicity following coronary revascularization by primary angioplasty for acute myocardial infarction study: design and rationale of the CONTRAST-AMI study. J Cardiovasc Med (Hagerstown). 2010 Mar;11(3):199-206. doi: 10.2459/JCM.0b013e32833186a4.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): February 10, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: October 12, 2015
• First Posted (Estimate): October 14, 2015

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 3, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Coronary angiography; Hypertension; Percutaneous coronary intervention; Contrast-induced nephropathy; Hyperhomocysteinemia
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Coronary Disease; Hypertension; Kidney Diseases; 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: lu 20143440