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

NCT02575092 | Completed Phase 2 DMC

• 1 other identifier: lu 20143440
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Homocysteine; Coronary Disease; Angioplasty,Balloon,Coronary; Contrast Media; Nephropathy; Hypertension

Keywords

Hyperhomocysteinemia; Coronary angiography; Percutaneous coronary intervention; Hypertension; Contrast-induced nephropathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Dialysis

  Within the first 3 months after procedure.

• Ischemic stroke

  Within the first 3 months after procedure.

• All cause mortality

  Within the first 3 months after procedure.

Study Arms (3)

Group A, without hypertension

ACTIVE COMPARATOR

The patients who will not be taken the drugs of antihypertension and antihomocysteine.

Drug: Placebo

Group B, hypertension

EXPERIMENTAL

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)

Group C,hypertension and hyperhomocysteinemia

EXPERIMENTAL

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)

Interventions

Enalapril Maleate Tablets(as the program-based antihypertension) DRUG

Group B, hypertension

Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension) DRUG

Group C,hypertension and hyperhomocysteinemia

Placebo DRUG

Group A, without hypertension

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fuling Central Hospital of Chongqing City: lead

Study Sites (1)

TIAN Jie

Fuling, Chongqing Municipality, 408099, China

Location

Related Publications (2)

• 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.

  PMID: 21791335 RESULT

• 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.

  PMID: 19829124 RESULT

MeSH Terms

Conditions

Coronary Disease; Kidney Diseases; Hypertension; Hyperhomocysteinemia

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Malabsorption Syndromes; Metabolic Diseases; Nutritional and Metabolic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Geriatrics

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 14, 2015
• Study Start: November 1, 2015
• Primary Completion: February 10, 2019
• Study Completion: July 31, 2019
• Last Updated: August 6, 2019

Record last verified: 2019-08

Locations

CN (1)