HomocysteinePhase 2/3CONTRAST-CADTNCT02575092
The Relationship Between HHcy and Contrast-induced Nephropathy in Hypertensive Patients After Coronary Artery Diagnosis and Treatment
A Phase 2/3 study testing Enalapril Maleate Tablets(as the program-based antihypertension) and Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension) in people with Homocysteine and Coronary Disease, run by Fuling Central Hospital of Chongqing City at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Homocysteine, Coronary Disease, Angioplasty,Balloon,Coronary
- What is being tested?
- Enalapril Maleate Tablets(as the program-based antihypertension) and Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,000 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2015to 31 Jul 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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%.
Show all 9Show fewer
- Secondary hypertension.
- Who can not be tolerated ACEI.
- Any other surgical contraindications.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Homocysteine, Coronary Disease, Angioplasty,Balloon,Coronary, Contrast Media, Nephropathy, Hypertension
- Being tested
- Enalapril Maleate Tablets(as the program-based antihypertension), Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension), Placebo
- Keywords
- Hyperhomocysteinemia, Coronary angiography, Percutaneous coronary intervention, Hypertension, Contrast-induced nephropathy
- Medical subject headings
- Coronary Disease, Kidney Diseases, Hypertension, Hyperhomocysteinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enalapril Maleate Tablets(as the program-based antihypertension)Drug
Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension)Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Group A, without hypertension | Active comparator | The patients who will not be taken the drugs of antihypertension and antihomocysteine. Receives: 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) Receives: 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) Receives: Drug: Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 48 hours after the procedure.
Secondary outcomes (3)
Dialysis
The hypertensive patients in the 3 groups who had been diagnosed as CIN need to dialysis.
Measured: 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
Measured: Within the first 3 months after procedure.
All cause mortality
Any cause of death in patients
Measured: Within the first 3 months after procedure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2015 (estimated)
- Study start1 Nov 2015
- Primary completion10 Feb 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HomocysteineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 4,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fuling Central Hospital of Chongqing City
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lu Jian-gang,MD, Fuling Central Hospital of Chongqing City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575092
- Sponsor's protocol ID
- lu 20143440
- Acronym
- CONTRAST-CADT
- Status last verified
- Aug 2019
- First submitted
- 12 Oct 2015
- Last updated
- 6 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 21791335Bolognese 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.
PubMed 19829124
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Department of Geriatrics
- ClinicalTrials.gov ID
- NCT02575092
- Acronym / sponsor ID
- CONTRAST-CADT / lu 20143440
- Conditions
- Homocysteine, Coronary Disease, Angioplasty,Balloon,Coronary, Contrast Media, Nephropathy, Hypertension
- Keywords
- Hyperhomocysteinemia, Coronary angiography, Percutaneous coronary intervention, Hypertension, Contrast-induced nephropathy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,000 participants (actual)
- Lead sponsor
- Fuling Central Hospital of Chongqing CityUniversity, hospital or other
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 10 Feb 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 14 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A, without hypertension | Active comparator | Drug: PlaceboThe patients who will not be taken the drugs of antihypertension and antihomocysteine. |
| Group B, hypertension | Experimental | Drug: 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(Enalapril Maleate Tablets,as the program-based antihypertension) |
| Group C,hypertension and hyperhomocysteinemia | Experimental | Drug: Enalapril Maleate and Folic Acid 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) |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
The incidence of contrast-induced nephropathy
Time frame: At 48 hours after the procedure.
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.
3 secondary outcomes
Dialysis
Time frame: Within the first 3 months after procedure.
Ischemic stroke
Time frame: Within the first 3 months after procedure.
All cause mortality
Time frame: Within the first 3 months after procedure.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
- Results publication: PubMed 21791335Kim 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 publication: PubMed 19829124Bolognese 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Enalapril Maleate Tablets(as the program-based antihypertension) and Enalapril Maleate and Folic Acid tablets(as the program-based antihypertension) in people with Homocysteine and Coronary Disease, run by Fuling Central Hospital of Chongqing City at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of contrast-induced nephropathy (time frame: At 48 hours after the procedure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02575092, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.