Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00732069
First received: August 6, 2008
Last updated: June 22, 2013
Last verified: June 2013

August 6, 2008
June 22, 2013
August 2008
December 2011   (final data collection date for primary outcome measure)
Interleukin 1 Beta [ Time Frame: During dialysis after one week of study drug ] [ Designated as safety issue: No ]
Mean difference in interleukin 1 beta concentration during treatment with ramipril versus treatment with placebo
To compare the effect of ACE inhibition or AT1 receptor blockade versus placebo on the fibrinolytic, oxidative stress and inflammatory response to hemodialysis [ Time Frame: end of each study ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00732069 on ClinicalTrials.gov Archive Site
F2-Isoprostanes [ Time Frame: During dialysis after one week of study drug ] [ Designated as safety issue: No ]
Mean difference in F2-isoprostanes during dialysis between treatment with ramipril or valsartan and placebo
To compare the effect of ACE inhibition versus AT1 receptor blockade on the fibrinolytic, oxidative stress and inflammatory response to hemodialysis [ Time Frame: end of each study ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis
Genes, Fibrinolysis and Endothelial Dysfunction- Dialysis Aim 2

Little is known about how some drugs affect inflammation or clotting factors in people receiving hemodialysis. It is not yet known if these drugs help prevent heart damage as they do in people not undergoing hemodialysis or whether they could increase the risk of heart problems. The purpose of the study is to measure certain chemicals in the blood and see how those chemicals may change during hemodialysis when certain drugs are given.

  • Cardiovascular disease in the leading cause of death in patients with chronic kidney disease undergoing hemodialysis.
  • Traditional risk factors do not adequately predict cardiovascular morbidity and mortality in patients with chronic kidney disease.
  • Increased oxidative stress, inflammation and impaired fibrinolysis contribute to cardiovascular risk in chronic kidney disease patients undergoing hemodialysis.
  • Activation of the renin-angiotensin-aldosterone system(RAAS) may contribute to oxidative stress and inflammation in individuals with chronic kidney disease
  • Activation of the kallikrein-kinin system during hemodialysis may increase fibrinolysis but may also contribute to inflammation in chronic kidney disease
  • Despite data from clinical trials demonstrating that ARBs and ACE inhibitors decrease cardiovascular mortality, delay progression to cardiovascular disease and decrease the incidence of diabetes in the general population little is known about the impact of these agents on cardiovascular morbidity and mortality in patients with end- stage renal disease (ESRD) undergoing hemodialysis
  • Angiotensin-converting enzyme(ACE) inhibitors and angiotensin receptor blockers (ARB)S differ in their mechanisms of action and their effects on inflammatory biomarkers
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • End Stage Renal Failure on Dialysis
  • Complication of Hemodialysis
  • Drug: Placebo
    Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks. Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period. Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days. Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days. On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
    Other Name: matching placebo
  • Drug: Ramipril
    Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks. Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period. Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days. Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days. On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
    Other Name: Ramipril 2.5mg/d for two days, then 5mg/d for 5 days.
  • Drug: Valsartan
    Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks. Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period. Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days. Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days. On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
    Other Name: Valsartan 80mg/d for 2 days followed by 160mg/d for 5 days.
  • Active Comparator: Placebo, then ramipril, then valsartan
    placebo, ramipril, valsartan: Subjects were treated sequentially with placebo, ramipril (5mg/day by mouth), then valsartan (160mg/day by mouth). Each drug was given for 7 days after a 3-week washout.
    Interventions:
    • Drug: Placebo
    • Drug: Ramipril
    • Drug: Valsartan
  • Active Comparator: Placebo, then valsartan, then ramipril
    placebo, ramipril, valsartan: Subjects were treated sequentially with placebo, valsartan (160mg/day by mouth), then ramipril (5mg/day by mouth). Each drug was given for 7 days after a 3-week washout.
    Interventions:
    • Drug: Placebo
    • Drug: Ramipril
    • Drug: Valsartan
  • Active Comparator: Ramipril, then placebo, then valsartan
    placebo, ramipril, valsartan: Subjects were treated sequentially with ramipril (5mg/day by mouth), then placebo (once a day by mouth), then valsartan (160mg/day by mouth). Each drug was given for 7 days after a 3-week washout.
    Interventions:
    • Drug: Placebo
    • Drug: Ramipril
    • Drug: Valsartan
  • Active Comparator: Valsartan, then placebo, then ramipril
    placebo, ramipril, valsartan: Subjects were treated sequentially with valsartan (160mg/day by mouth), then placebo (once a day by mouth), then ramipril (5mg/day by mouth). Each drug was given for 7 days after a 3-week washout.
    Interventions:
    • Drug: Placebo
    • Drug: Ramipril
    • Drug: Valsartan
  • Active Comparator: Ramipril, then valsartan, then placebo
    placebo, ramipril, valsartan: Subjects were treated sequentially with ramipril (5mg/day by mouth), then valsartan (160mg/day by mouth), then placebo (once a day by mouth). Each drug was given for 7 days after a 3-week washout.
    Interventions:
    • Drug: Placebo
    • Drug: Ramipril
    • Drug: Valsartan
  • Active Comparator: Valsartan, then ramipril, then placebo
    placebo, ramipril, valsartan: Subjects were treated sequentially with then valsartan (160mg/day by mouth), then ramipril (5mg/day by mouth), then placebo (once a day by mouth). Each drug was given for 7 days after a 3-week washout.
    Interventions:
    • Drug: Placebo
    • Drug: Ramipril
    • Drug: Valsartan
Gamboa JL, Pretorius M, Todd-Tzanetos DR, Luther JM, Yu C, Ikizler TA, Brown NJ. Comparative effects of angiotensin-converting enzyme inhibition and angiotensin-receptor blockade on inflammation during hemodialysis. J Am Soc Nephrol. 2012 Feb;23(2):334-42. doi: 10.1681/ASN.2011030287. Epub 2011 Dec 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
December 2011
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 18 years or older
  • On thrice-weekly chronic hemodialysis for at least 6 months
  • Clinically stable, adequately dialyzed (single-pool Kt/V> 1.2) thrice weekly, with polysulphone membrane for at least 3 consecutive months prior to study

Exclusion Criteria:

  • Body mass index > 35 mg/kg
  • History of functional transplant less than 6 months prior to study
  • Use of anti-inflammatory medications other than aspirin < 325 mg/d
  • History of active connective tissue disease
  • History of acute infectious disease within one month prior to study
  • AIDS (HIV seropositivity is not an exclusion criteria)
  • History of myocardial infarction or cerebrovascular event within 3 months
  • Advanced liver disease
  • Gastrointestinal dysfunction requiring parental nutrition
  • Active malignancy excluding basal cell carcinoma of the skin
  • History of ACE inhibitor-associated cough or angioedema
  • Ejection fraction less than 40%
  • Inability to discontinue ACE inhibitor or ARB
  • Predialysis potassium repeatedly higher than 5.5 mmol/L (confirmed on a repeated blood draw)
  • Anticipated live donor kidney transplant
  • Use of vitamin E >60 IU/d or vitamin C >500 mg/d
  • Pregnancy, breast-feeding or child-bearing potential
  • History of poor adherence to hemodialysis or medical regimen
  • Inability to provide consent
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00732069
Fibrinolysis in Dialysis, R01HL065193-08A2
Yes
Nancy J. Brown, Vanderbilt University
Vanderbilt University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Nancy J Brown, MD Vanderbilt University
Vanderbilt University
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP