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Kidney Transplant Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Ottawa Hospital Research Institute
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
St. Paul's Hospital, Canada
Vancouver General Hospital
Kingston General Hospital
University of Saskatchewan
University of Calgary
University of Manitoba
University Health Network, Toronto
St. Michael's Hospital, Toronto
St. Joseph's Healthcare Hamilton
London Health Sciences Centre
McGill University Health Center
Maisonneuve-Rosemont Hospital
Centre hospitalier de l'Université de Montréal (CHUM)
Centre Hospitalier Universitaire de Québec, CHU de Québec
University of Alberta
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01296061
First received: February 8, 2011
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

Primary Hypotheses:

  1. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have more deaths than patients who discontinue these drugs
  2. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have more hospitalizations for sepsis than patients who discontinue these drugs
  3. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have fewer rejection events than patients who discontinue these drugs

Secondary Hypotheses:

  1. Patients who undergo elective nephrectomy (to remove the failed kidney transplant) will have fewer deaths than those who retain the failed kidney transplant
  2. Patients who undergo elective nephrectomy (to remove the failed kidney transplant) will have fewer hospitalizations for sepsis than those who retain the failed kidney transplant
  3. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have lower levels of allosensitization (anti-HLA antibodies) than those who discontinue these drugs
  4. Patients who undergo elective nephrectomy will have higher levels of allosensitization (anti-HLA antibodies) than patients who retain the failed kidney transplant

Condition
Acute Graft Rejection
Renal Failure Chronic Requiring Dialysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of Immunosuppressive Medication Use on Patient Outcomes Following Kidney Transplantation Failure

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Death [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Death: Death will be identified through monthly contact of study coordinators with the treating dialysis center. Date of death will be obtained from records maintained by dialysis programs. If required, the patient's treating physician may contact the next of kin to confirm the date of death.

  • Sepsis [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Sepsis: Hospital discharge records will be reviewed for the most responsible diagnosis. Hospitalizations for sepsis will be identified if an infection is recorded as the primary or secondary discharge diagnosis, and confirmatory laboratory evidence of infection (i.e. positive culture or chest radiograph compatible with pneumonia) is present. In the absence of laboratory evidence of infection, documentation of clinical sign or symptoms of infection will be required (fever, shock, localizing symptoms). The source of infection (e.g. catheter related, urinary tract etc) will be documented.

  • Rejection of failed allograft. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Rejection of failed allograft: After transplant failure, rejection is rarely confirmed by a biopsy of the allograft. Rejection events will be identified by patient interview and clinical chart review during follow up visits. Rejection will be identified when both a diagnosis of rejection with compatible signs/ symptoms is documented and either an increase in immunosuppressant drugs is prescribed, or transplant nephrectomy is performed. Only rejection events diagnosed after the initiation of dialysis will be included.

  • Allosensitization [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Allosensitization: Serum samples will be collected at baseline and at each study visit. Dialysis centers routinely collect serum samples for monitoring allosensitization in wait-listed transplant candidates and have established local protocols for collection, storage and shipping. Both class I and class II Anti-HLA antibodies will be appraised using FlowPRA®.


Biospecimen Retention:   Samples Without DNA

Class I and II HLA antibodies


Estimated Enrollment: 920
Study Start Date: August 2011
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Failed Kidney Transplant
Adults ≥ 18 years, initiating chronic dialysis

Detailed Description:

Transplantation is the best treatment for patients with end stage kidney disease.1 However, despite the development of powerful immunosuppressant medications, transplantation still does not provide most patients with lifelong freedom from dialysis. The half-life (time to 50% failure) of a deceased donor kidney transplant is only 10.5 years.4, 5 As the number of prevalent patients who received a transplant more than a decade ago increases, the number of patients with failing transplants who must either return to dialysis or undergo repeat transplantation is also rapidly increasing.6 Repeat transplantation is clearly the best option for these patients.8 However, in Canada, only 10% of patients with first transplant failure will receive a second transplant.9 Consequently transplant failure is now the fifth leading individual cause of dialysis initiation in Canada.6, 10 Survival after transplant failure is very poor, with 40% mortality in the first 5 years after initiation of dialysis.9, 11, 12 In comparison, the 5 year mortality of de novo incident dialysis patients, including those who are not even transplant candidates, is 50%, 6, 10while that of first transplant recipients is < 10%.6, 10 However, the unique characteristics of the transplant failure population limit the validity of such comparisons with other chronic kidney disease patients. Transplant failure patients were initially selected to undergo transplantation because of their favorable age and health status, and thus differ from unselected de novo incident dialysis patients. Similarly, unlike first time transplant recipients, transplant failure patients already have prolonged exposure to immunosuppressant medications that can increase the risk of cardiovascular disease, cancer and metabolic bone disease. Notwithstanding these issues, we and others have published a number of studies documenting the poor outcomes, and stressing the need for prospective studies in this unique subset of chronic kidney disease patients.9, 12-16 To date, no study has systematically examined this patient population and basic questions about how to manage the failed kidney allograft remain. Although there are some clear indications for emergent surgical removal of the failed allograft (nephrectomy), the elective use of nephrectomy is highly variable and poorly described.17-19 Acute immunologic injury (rejection) in the failed transplant can occur as long as the allograft remains in situ, and can cause both local and systemic symptoms. In addition, the failed allograft may promote chronic inflammation leading to malnutrition, anemia and cardiovascular disease.20, 21 No prospective studies have examined whether nephrectomy and discontinuation of immunosuppressant medications is preferable to retaining the failed allograft. If the allograft is retained, it is not known whether the risk of continued exposure to immunosuppressant medications outweighs the risk of acute rejection or chronic inflammation when these drugs are discontinued. Importantly, management of the failed allograft can impact allosensitization,22-24 a primary determinant of a patient's ability to undergo repeat transplantation.

This prospective observational study is a necessary first step in defining the optimal management strategy for this unique and growing patient population. The primary and secondary research questions will determine the association of (i) immunosuppressant drug use and (ii) elective nephrectomy with clinical outcomes including death, sepsis, and rejection. Importantly, the study will also determine the association of these exposures with allosensitization (anti-HLA antibodies). The information obtained will inform the design of future interventional studies that will definitively define how to best manage these complex patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients ≥ 18 years, who initiate chronic dialysis treatment after failure of a first kidney transplant

Criteria

Inclusion Criteria:Patients ≥ 18 years, who initiate chronic dialysis treatment after failure of a first kidney transplant

Exclusion Criteria:Recipients of a multi-organ transplant (e.g. kidney- pancreas transplant), and patients unable to provide informed consent.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296061

Contacts
Contact: Greg Knoll, MD 613-738-8400 ext 82536 gknoll@ottawahospital.on.ca
Contact: Debora Hogan, M.Sc.N. 613-737-8899 ext 71297 dhogan@ohri.ca

Locations
Canada, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Debora Hogan, M.Sc.N.    613-737-8899 ext 71297    dhogan@ohri.ca   
Contact: Erin Murphy    613-737-8899 ext 73580    emurphy@ohri.ca   
Principal Investigator: Greg Knoll, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Canadian Institutes of Health Research (CIHR)
St. Paul's Hospital, Canada
Vancouver General Hospital
Kingston General Hospital
University of Saskatchewan
University of Calgary
University of Manitoba
University Health Network, Toronto
St. Michael's Hospital, Toronto
St. Joseph's Healthcare Hamilton
London Health Sciences Centre
McGill University Health Center
Maisonneuve-Rosemont Hospital
Centre hospitalier de l'Université de Montréal (CHUM)
Centre Hospitalier Universitaire de Québec, CHU de Québec
University of Alberta
Investigators
Principal Investigator: Greg Knoll, MD U of Ottawa, The Ottawa Hospital, OHRI
Principal Investigator: John Gill, MD UBC, St Paul's Hospital Vancouver, BC
  More Information

No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01296061     History of Changes
Other Study ID Numbers: CIHR FRN MOP-102732
Study First Received: February 8, 2011
Last Updated: October 14, 2014
Health Authority: Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
Dialysis
Renal Transplantation
Failure of allograft

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases

ClinicalTrials.gov processed this record on November 23, 2014