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Kidney DiseasePhase 4NCT00067990

Angiotensin II Blockade for Chronic Allograft Nephropathy

A Phase 4 study testing Losartan 100mg in people with Kidney Disease and Proteinuria, run by University of Minnesota at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Kidney Disease, Proteinuria
What is being tested?
Losartan 100mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
153 participants
Where
2 sitesUnited States
Study dates
Dec 2002to Jun 2011
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Angiotensin II Blockade for the Prevention of Cortical Interstitial Expansion and Graft Loss in Kidney Transplant Recipients

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.

Read the detailed description

Renal transplant loss due to chronic allograft nephropathy (CAN) is widely acknowledged as a major problem that has increased in relative importance as the incidence of early graft loss from acute rejection has declined. Studies from various centers, including the University of Minnesota, suggest that, after excluding patients dying with a functioning graft, as many as 80% of patients who will return to dialysis do so because of CAN. At the present time there are no therapeutic options once the clinical manifestations of CAN have developed. Testing measures to prevent CAN have not been addressed.

The overall purpose of this project is to investigate the role of the renin-angiotensin-aldosterone system (RAAS) in the development of CAN. This system plays an important role in the progression of many experimental and clinical renal diseases. Furthermore, blockade of this system with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. This study specifically investigates the long term benefit of the angiotensin II receptor blocker, losartan, in the prevention of cortical interstitial volume expansion (an accurate predictor of long term graft function) and graft loss from biopsy proven CAN in a 5 year, randomized, double masked, placebo controlled study of kidney transplant recipients. This clinical trial will directly test the hypothesis that blockade of the renin angiotensin aldosterone system will provide a substantial benefit through blood pressure lowering independent mechanisms, namely, interruption of fibrogenic pathways, anti-proteinuric actions, amelioration of hyperfiltration and possibly some immunomodulatory effects.

The proposed studies will also characterize the interstitial ultrastructural compositional changes that occur in the renal allografts with CAN, the effects of treatment on these changes and provide a complete description of the incidence and predictors for the development of transplant glomerulopathy. These studies will also determine the impact of angiotensin II receptor blockade on the rate of decline of glomerular filtration rate, as well as the impact of glomerular size on the rate of graft loss from CAN, the incidence and the progression of post transplant proteinuria, the nature of the permselectivity defects responsible for the proteinuria and will also explore the association of proteinuria with graft loss from CAN. This trial will also help construct a profile for the RAAS in the transplant recipients and explore the relationship between two genes polymorphisms, ACE and TGF-Beta, and CAN.

These studies should help to describe the natural history, nature and pathogenesis of CAN, elucidate early markers and predictors of this important disorder and, perhaps, define a safe and useful preventative strategy.

Being tested
Losartan 100mg, Placebo
Keywords
chronic allograft nephropathy, post transplant proteinuria
Medical subject headings
Kidney Diseases, Proteinuria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Losartan 100mgDrug

    Also called Losartan

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

  • PlaceboDrug

    No treatment with continued follow-up for five years.

Study groups in NCT00067990
Study groupRoleWhat they receive
Losartan 100mgExperimentalLosartan 100 mg per day to be started within three months of transplantation and continuing treatment for five years.
Receives: Drug: Losartan 100mg
PlaceboPlacebo comparatorNo intervention with continuing follow-up for five years.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Doubling of Interstitium or Any ESRD

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

    Measured: Baseline to 5 years

Secondary outcomes (1)

  1. Number of Participants With Cortical Interstitial Volume Expansion or Any ESRD

    Number of subjects who had doubling of the interstitial or any end stage renal disease (ESRD) not attributed to interstitial fibrosis and tubular atrophy (IF/TA)

    Measured: Baseline and 5 Years Post Transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2003 (estimated)
  2. Study startDec 2002
  3. Primary completionJun 2011
  4. Study completionJun 2011

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00067990
Sponsor's protocol ID
ANGIOB
Other IDs
R01DK060706
Status last verified
Sep 2017
First submitted
3 Sep 2003
Last updated
18 Sep 2017
Data monitoring committee
Yes
Individual data sharing
No: There are no plans to share individual participant data.

Publications

  • 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.

    PubMed 23308016

  • 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.

    PubMed 39082471

  • 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.

    PubMed 24457184

  • 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.

    PubMed 23965522

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Losartan 100mg in people with Kidney Disease and Proteinuria, run by University of Minnesota at 2 sites in United States.

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 4 inclusion and 10 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 18 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 18 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Doubling of Interstitium or Any ESRD (time frame: Baseline to 5 years). 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 NCT00067990, 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 18 Sep 2017.

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