Angiotensin II Blockade for Chronic Allograft Nephropathy

NCT00067990 | Completed Phase 4 Results DMC

• 2 other identifiers: ANGIOBR01DK060706
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 2

Brief Summary

Chronic allograft nephropathy continues to be a major cause of kidney transplant loss and return to dialysis. Treatment options are limited and the course of the disease tends to be progressive. This trial is designed to prevent a major mediator of this process, namely the expansion of the cortical interstitial compartment of the kidney where most of the scarring occurs. The drug being studied, Losartan, has proven efficacious in a number of kidney diseases.

Conditions

Kidney Disease; Proteinuria

Keywords

chronic allograft nephropathy; post transplant proteinuria

Outcome Measures

Primary Outcomes (1)

• Doubling of Interstitium or Any ESRD

  Doubling of the interstitial or any defined ESRD (including IF/TA)

  Baseline to 5 years

Secondary Outcomes (1)

• Number of Participants With Cortical Interstitial Volume Expansion or Any ESRD

  Baseline and 5 Years Post Transplant

Study Arms (2)

Losartan 100mg

EXPERIMENTAL

Losartan 100 mg per day to be started within three months of transplantation and continuing treatment for five years.

Drug: Losartan 100mg

Placebo

PLACEBO COMPARATOR

No intervention with continuing follow-up for five years.

Drug: Placebo

Interventions

Losartan 100mg DRUG

To be started within three months of transplant and continued for five years.

Also known as: Losartan

Losartan 100mg

Placebo DRUG

No treatment with continued follow-up for five years.

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.
• Recipients of a first or a second renal transplant alone or in combination with a pancreas transplantation.
• Informed consent
• Adequate baseline biopsy; at least 10 cortical projection fields.

You may not qualify if:

• Age \< 18 years.
• Serum creatinine 2.5mg/dL.
• Persistent hyperkalemia; potassium \> 5.4 mEq/L.
• Known hypersensitivity to losartan or iodine allergy.
• Documented renal artery stenosis by duplex ultrasonography.
• Recipients of grafts from an HLA-identical sibling.
• Recipients whose primary renal disease is primary hyperoxaluria,dense-deposit disease, focal segmental glomerulosclerosis or hemolytic uremic syndrome.
• Women of childbearing age who wish to become pregnant and/or are unwilling to use contraceptive measures or who are pregnant.
• Recipients requiring ACE inhibitors or AII blockers for a cardiovascular indication (e.g. systolic dysfunction).
• Recipients who are \> 55 years old and had a history of cardiovascular disease (coronary artery disease, stroke or peripheral vascular disease).

Sponsors & Collaborators

• University of Minnesota: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (4)

• Ibrahim HN, Jackson S, Connaire J, Matas A, Ney A, Najafian B, West A, Lentsch N, Ericksen J, Bodner J, Kasiske B, Mauer M. Angiotensin II blockade in kidney transplant recipients. J Am Soc Nephrol. 2013 Feb;24(2):320-7. doi: 10.1681/ASN.2012080777. Epub 2013 Jan 10.

  PMID: 23308016 BACKGROUND

• Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.

  PMID: 39082471 DERIVED

• Kukla A, Issa N, Jackson S, Spong R, Foster MC, Matas AJ, Mauer MS, Eckfeldt JH, Ibrahim HN. Cystatin C enhances glomerular filtration rate estimating equations in kidney transplant recipients. Am J Nephrol. 2014;39(1):59-65. doi: 10.1159/000357594. Epub 2014 Jan 18.

  PMID: 24457184 DERIVED

• Issa N, Ortiz F, Reule SA, Kukla A, Kasiske BL, Mauer M, Jackson S, Matas AJ, Ibrahim HN, Najafian B. The renin-aldosterone axis in kidney transplant recipients and its association with allograft function and structure. Kidney Int. 2014 Feb;85(2):404-15. doi: 10.1038/ki.2013.278. Epub 2013 Aug 21.

  PMID: 23965522 DERIVED

MeSH Terms

Conditions

Kidney Diseases; Proteinuria

Interventions

Losartan

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Hassan N. Ibrahim, MD
• Organization: University_of_Minnesota

ibrah007@umn.edu

(612) 624-9444

Study Officials

• Hassan N. Ibrahim, M.D., M.S.

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Bertram Kasiske, M.D.

  Hennepin County Medical Center, Minneapolis

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2003
• First Posted: September 5, 2003
• Study Start: December 1, 2002
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 18, 2017
• Results First Posted: September 18, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)