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

Primary Purpose

Homocysteine, Coronary Disease, Angioplasty,Balloon,Coronary

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Enalapril Maleate Tablets(as the program-based antihypertension)
Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension)
Placebo
Sponsored by
Fuling Central Hospital of Chongqing City
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Homocysteine focused on measuring Hyperhomocysteinemia, Coronary angiography, Percutaneous coronary intervention, Hypertension, Contrast-induced nephropathy

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • TIAN Jie

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Group A, without hypertension

Group B, hypertension

Group C,hypertension and hyperhomocysteinemia

Arm Description

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

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)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Dialysis
The hypertensive patients in the 3 groups who had been diagnosed as CIN need to dialysis.
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
All cause mortality
Any cause of death in patients

Full Information

First Posted
October 12, 2015
Last Updated
August 3, 2019
Sponsor
Fuling Central Hospital of Chongqing City
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1. Study Identification

Unique Protocol Identification Number
NCT02575092
Brief Title
The Relationship Between HHcy and Contrast-induced Nephropathy in Hypertensive Patients After Coronary Artery Diagnosis and Treatment
Acronym
CONTRAST-CADT
Official Title
Department of Geriatrics
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
November 1, 2015 (Actual)
Primary Completion Date
February 10, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fuling Central Hospital of Chongqing City

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Homocysteine, Coronary Disease, Angioplasty,Balloon,Coronary, Contrast Media, Nephropathy, Hypertension
Keywords
Hyperhomocysteinemia, Coronary angiography, Percutaneous coronary intervention, Hypertension, Contrast-induced nephropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
4000 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A, without hypertension
Arm Type
Active Comparator
Arm Description
The patients who will not be taken the drugs of antihypertension and antihomocysteine.
Arm Title
Group B, hypertension
Arm Type
Experimental
Arm Description
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)
Arm Title
Group C,hypertension and hyperhomocysteinemia
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Enalapril Maleate Tablets(as the program-based antihypertension)
Intervention Type
Drug
Intervention Name(s)
Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension)
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
The incidence of contrast-induced nephropathy
Description
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.
Time Frame
At 48 hours after the procedure.
Secondary Outcome Measure Information:
Title
Dialysis
Description
The hypertensive patients in the 3 groups who had been diagnosed as CIN need to dialysis.
Time Frame
Within the first 3 months after procedure.
Title
Ischemic stroke
Description
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
Time Frame
Within the first 3 months after procedure.
Title
All cause mortality
Description
Any cause of death in patients
Time Frame
Within the first 3 months after procedure.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
TIAN Jie
City
Fuling
State/Province
Chongqing
ZIP/Postal Code
408099
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
21791335
Citation
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.
Results Reference
result
PubMed Identifier
19829124
Citation
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.
Results Reference
result

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

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