Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis

NCT00732069 | Completed Phase 2 Results DMC

• 2 other identifiers: Fibrinolysis in DialysisR01HL065193-08A2
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

End Stage Renal Failure on Dialysis; Complication of Hemodialysis

Keywords

hemodialysis; oxidative stress; inflammation; kallikrein-kinin; angiotensin receptor blockade; angiotensin converting enzyme inhibition; RAAS; fibrinolysis; endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• Interleukin 1 Beta

  Mean difference in interleukin 1 beta concentration during treatment with ramipril versus treatment with placebo

  During dialysis after one week of study drug

Secondary Outcomes (1)

• F2-Isoprostanes

  During dialysis after one week of study drug

Study Arms (6)

Placebo, then ramipril, then valsartan

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Ramipril; Drug: Valsartan

Placebo, then valsartan, then ramipril

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Ramipril; Drug: Valsartan

Ramipril, then placebo, then valsartan

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Ramipril; Drug: Valsartan

Valsartan, then placebo, then ramipril

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Ramipril; Drug: Valsartan

Ramipril, then valsartan, then placebo

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Ramipril; Drug: Valsartan

Valsartan, then ramipril, then placebo

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Ramipril; Drug: Valsartan

Interventions

Placebo DRUG

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

Also known as: matching placebo

Placebo, then ramipril, then valsartan; Placebo, then valsartan, then ramipril; Ramipril, then placebo, then valsartan; Ramipril, then valsartan, then placebo; Valsartan, then placebo, then ramipril; Valsartan, then ramipril, then placebo

Ramipril DRUG

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

Also known as: Ramipril 2.5mg/d for two days, then 5mg/d for 5 days.

Placebo, then ramipril, then valsartan; Placebo, then valsartan, then ramipril; Ramipril, then placebo, then valsartan; Ramipril, then valsartan, then placebo; Valsartan, then placebo, then ramipril; Valsartan, then ramipril, then placebo

Valsartan DRUG

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

Also known as: Valsartan 80mg/d for 2 days followed by 160mg/d for 5 days.

Placebo, then ramipril, then valsartan; Placebo, then valsartan, then ramipril; Ramipril, then placebo, then valsartan; Ramipril, then valsartan, then placebo; Valsartan, then placebo, then ramipril; Valsartan, then ramipril, then placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37323, United States

Location

Related Publications (2)

• 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.

  PMID: 22158433 RESULT

• Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA. Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study. BMC Nephrol. 2015 Oct 22;16:167. doi: 10.1186/s12882-015-0162-x.

  PMID: 26494370 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

Ramipril; Valsartan

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Dr. Nancy J. Brown
• Organization: Vanderbilt University

nancy.j.brown@vanderbilt.edu

615-343-8701

Study Officials

• Nancy J Brown, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 11, 2008
• Study Start: August 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 2, 2013
• Results First Posted: June 20, 2013

Record last verified: 2013-06

Locations

US (1)