Chronic Kidney DiseasePhase 4NCT00384618
Anti-Oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study
A Phase 4 study testing pravastatin and vitamin E in people with Chronic Kidney Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The ATIC study is a randomised, double- blind, placebo-controlled trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic non-diabetic renal failure who are free from manifest arterial occlusive disease. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- pravastatin and vitamin E
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2001to Aug 2005
- Phase
- Phase 4
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- kidney disease (clearence between 15-70ml/min)
Who cannot join
- diabetes mellitus (ADA criteria), active vasculitis, nephrotic syndrome (>3g protein/24h urine), renal transplantation, fasting total cholesterol > 7 mmol/L, cholesterol-lowering therapy within three months prior to inclusion or known ischaemic coronary, cerebrovascular or peripheral arterial disease
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1007 MB
About this study
Official title: Effect of an Oxidative-Stress-Reducing Strategy Consisting of Pravastatin, Vitamin E and Homocysteine-Lowering on Carotid Intima-Media Thickness in Patients With Mild-to-Moderate Chronic Kidney Disease
The ATIC study is a randomised, double- blind, placebo-controlled trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic non-diabetic renal failure who are free from manifest arterial occlusive disease. Participants in the trial were randomised to active treatment consisting of add-on therapy with pravastatin, vitamin E and homocysteine-lowering therapy, or to placebo. Subjects not using angiotensin converting enzyme inhibitors (ACE-inhibitors) or angiotensin receptor blockers (ARBs) at inclusion were put on ACE-inhibitors for at least two weeks before the baseline measurement and randomisation. Those who were on ARBs continued their ARBs. We excluded individuals with diabetes mellitus (ADA criteria), active vasculitis, nephrotic syndrome (>3gr/24hr urine protein), renal transplantation, fasting total cholesterol > 7 mmol/L, cholesterol-lowering therapy within three months prior to inclusion or known ischemic cardiac, cerebrovascular or peripheral arterial disease. Ninety-three patients (out of 118 eligible patients) took part in the study and written informed consent was obtained from all participants.
Read the detailed description
Background: Patients with mild-to-moderate renal failure have an increased risk of cardiovascular disease (CVD), which is not fully explained by the presence of classical cardiovascular risk factors. Oxidative stress has been proposed to play a major role in the development of CVD among renal failure patients. We investigated, in patients with mild-to-moderate chronic kidney disease (CKD), the effect of an oxidative-stress-lowering therapy with pravastatin, vitamin E and homocysteine-lowering on carotid intima-media thickness and endothelial function (two strong surrogate markers of cardiovascular risk), and renal function.
Methods: 93 patients with CKD (Cockcroft-Gault equation; mean: 41±17 ml / min per 1.73 m2) who were free of manifest arterial occlusive disease and diabetes mellitus were included in the Anti-oxidant Therapy In Chronic renal insufficiency (ATIC) study, a randomized, double-blind, placebo-controlled trial. The active treatment group received pravastatin 40 mg/day to which after 6 months vitamin E 300 mg/day was added and after another 6 months homocysteine-lowering therapy (folic acid 5 mg/day, pyridoxine 100 mg, vitamin B-12 1 mg/day). The placebo group received matching placebos at onset, and 6 and 12 months later. Blood pressure in both groups was managed according to a standard protocol to achieve a blood pressure of < 140/90 mmHg. Patients were followed up for two years. Measurements of common carotid artery intima-media thickness (CCA-IMT) and brachial artery endothelium-dependent, flow-mediated dilatation (BA-FMD) were performed at randomisation and after 6, 12 and 18 months. Plasma oxidized LDL (oxLDL) and plasma malondialdehyde (MDA) were measured as markers of oxidative stress at randomisation and after 6, 12, 18 and 24 months. We used generalized estimating equations (GEE) for data analysis.
- Conditions
- Chronic Kidney Disease
- Being tested
- pravastatin, vitamin E
- Keywords
- Kidney, Antioxidants, Statin, Carotid IMT
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pravastatinDrug
vitamin EDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Common carotid artery intima media thickness
Brachial artery flow mediated vasodilatation
Secondary outcomes (1)
Renal function
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startMay 2001
- Study completionAug 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Foundation, The Netherlands, Bristol-Myers Squibb
- Investigators
- Prof. Peter M ter Wee, MD, PhD, Study director, Depratment of Nephrology, VU University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384618
- Sponsor's protocol ID
- C97-1707
- Status last verified
- Oct 2006
- First submitted
- 4 Oct 2006
- Last updated
- 6 Oct 2006
- Results posted
- No
Publications
Nanayakkara PW, Teerlink T, Stehouwer CD, Allajar D, Spijkerman A, Schalkwijk C, ter Wee PM, van Guldener C. Plasma asymmetric dimethylarginine (ADMA) concentration is independently associated with carotid intima-media thickness and plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration in patients with mild-to-moderate renal failure. Kidney Int. 2005 Nov;68(5):2230-6. doi: 10.1111/j.1523-1755.2005.00680.x.
PubMed 16221223Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.
PubMed 37916745Nanayakkara PW, Kiefte-de Jong JC, ter Wee PM, Stehouwer CD, van Ittersum FJ, Olthof MR, Teerlink T, Twisk JW, van Guldener C, Smulders YM. Randomized placebo-controlled trial assessing a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on plasma asymmetric dimethylarginine concentration in mild to moderate CKD. Am J Kidney Dis. 2009 Jan;53(1):41-50. doi: 10.1053/j.ajkd.2008.06.016. Epub 2008 Sep 11.
PubMed 18786751Nanayakkara PW, van Guldener C, ter Wee PM, Scheffer PG, van Ittersum FJ, Twisk JW, Teerlink T, van Dorp W, Stehouwer CD. Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study. Arch Intern Med. 2007 Jun 25;167(12):1262-70. doi: 10.1001/archinte.167.12.1262.
PubMed 17592099
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of an Oxidative-Stress-Reducing Strategy Consisting of Pravastatin, Vitamin E and Homocysteine-Lowering on Carotid Intima-Media Thickness in Patients With Mild-to-Moderate Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT00384618
- Acronym / sponsor ID
- C97-1707
- Conditions
- Chronic Kidney Disease
- Keywords
- Kidney, Antioxidants, Statin, Carotid IMT
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 100 participants
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Medical Research Foundation, The Netherlands, Bristol-Myers Squibb
- Study start
- May 2001
- Study completion
- Aug 2005
- First posted
- 6 Oct 2006 (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.
The ATIC study is a randomised, double- blind, placebo-controlled trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic non-diabetic renal failure who are free from manifest arterial occlusive disease. Participants in the trial were randomised to active treatment consisting of add-on therapy with pravastatin, vitamin E and homocysteine-lowering therapy, or to placebo. Subjects not using angiotensin converting enzyme inhibitors (ACE-inhibitors) or angiotensin receptor blockers (ARBs) at inclusion were put on ACE-inhibitors for at least two weeks before the baseline measurement and randomisation. Those who were on ARBs continued their ARBs. We excluded individuals with diabetes mellitus (ADA criteria), active vasculitis, nephrotic syndrome (>3gr/24hr urine protein), renal transplantation, fasting total cholesterol > 7 mmol/L, cholesterol-lowering therapy within three months prior to inclusion or known ischemic cardiac, cerebrovascular or peripheral arterial disease. Ninety-three patients (out of 118 eligible patients) took part in the study and written informed consent was obtained from all participants.
Detailed description
Background: Patients with mild-to-moderate renal failure have an increased risk of cardiovascular disease (CVD), which is not fully explained by the presence of classical cardiovascular risk factors. Oxidative stress has been proposed to play a major role in the development of CVD among renal failure patients. We investigated, in patients with mild-to-moderate chronic kidney disease (CKD), the effect of an oxidative-stress-lowering therapy with pravastatin, vitamin E and homocysteine-lowering on carotid intima-media thickness and endothelial function (two strong surrogate markers of cardiovascular risk), and renal function.
Methods: 93 patients with CKD (Cockcroft-Gault equation; mean: 41±17 ml / min per 1.73 m2) who were free of manifest arterial occlusive disease and diabetes mellitus were included in the Anti-oxidant Therapy In Chronic renal insufficiency (ATIC) study, a randomized, double-blind, placebo-controlled trial. The active treatment group received pravastatin 40 mg/day to which after 6 months vitamin E 300 mg/day was added and after another 6 months homocysteine-lowering therapy (folic acid 5 mg/day, pyridoxine 100 mg, vitamin B-12 1 mg/day). The placebo group received matching placebos at onset, and 6 and 12 months later. Blood pressure in both groups was managed according to a standard protocol to achieve a blood pressure of < 140/90 mmHg. Patients were followed up for two years. Measurements of common carotid artery intima-media thickness (CCA-IMT) and brachial artery endothelium-dependent, flow-mediated dilatation (BA-FMD) were performed at randomisation and after 6, 12 and 18 months. Plasma oxidized LDL (oxLDL) and plasma malondialdehyde (MDA) were measured as markers of oxidative stress at randomisation and after 6, 12, 18 and 24 months. We used generalized estimating equations (GEE) for data analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- kidney disease (clearence between 15-70ml/min)
Key exclusion criteria (1 listed)
- diabetes mellitus (ADA criteria), active vasculitis, nephrotic syndrome (>3g protein/24h urine), renal transplantation, fasting total cholesterol > 7 mmol/L, cholesterol-lowering therapy within three months prior to inclusion or known ischaemic coronary, cerebrovascular or peripheral arterial disease
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 |
|---|---|---|
| pravastatin | Drug | – |
| vitamin E | Drug | – |
Primary outcome
Common carotid artery intima media thickness
Brachial artery flow mediated vasodilatation
1 secondary outcome
Renal function
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2006.
- Results publication: PubMed 16221223Nanayakkara PW, Teerlink T, Stehouwer CD, Allajar D, Spijkerman A, Schalkwijk C, ter Wee PM, van Guldener C. Plasma asymmetric dimethylarginine (ADMA) concentration is independently associated with carotid intima-media thickness and plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration in patients with mild-to-moderate renal failure. Kidney Int. 2005 Nov;68(5):2230-6. doi: 10.1111/j.1523-1755.2005.00680.x.
- Derived from this study: PubMed 37916745Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.
- Derived from this study: PubMed 18786751Nanayakkara PW, Kiefte-de Jong JC, ter Wee PM, Stehouwer CD, van Ittersum FJ, Olthof MR, Teerlink T, Twisk JW, van Guldener C, Smulders YM. Randomized placebo-controlled trial assessing a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on plasma asymmetric dimethylarginine concentration in mild to moderate CKD. Am J Kidney Dis. 2009 Jan;53(1):41-50. doi: 10.1053/j.ajkd.2008.06.016. Epub 2008 Sep 11.
- Derived from this study: PubMed 17592099Nanayakkara PW, van Guldener C, ter Wee PM, Scheffer PG, van Ittersum FJ, Twisk JW, Teerlink T, van Dorp W, Stehouwer CD. Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study. Arch Intern Med. 2007 Jun 25;167(12):1262-70. doi: 10.1001/archinte.167.12.1262.
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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.
Prof. Peter M ter Wee, MD, PhD study director
Depratment of Nephrology, VU University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing pravastatin and vitamin E in people with Chronic Kidney Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 1 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: stopped early, as of the sponsor's last update on 6 Oct 2006. 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 Netherlands. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early. Results are not available in the source record.
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?
Common carotid artery intima media thickness. The study lists 2 primary outcomes in all. 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 NCT00384618, which also lists 4 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 Oct 2006.