Acute Graft RejectionNCT01296061
Kidney Transplant Failure
An observational study of Acute Graft Rejection and Renal Failure Chronic Requiring Dialysis, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Graft Rejection, Renal Failure Chronic Requiring Dialysis
- How many people
- 270 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2011to Jul 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Patients ≥ 18 years, who initiate chronic dialysis treatment after failure of a first kidney transplant
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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Immunosuppressive Medication Use on Patient Outcomes Following Kidney Transplantation Failure
Primary Hypotheses:
- Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have more deaths than patients who discontinue these drugs
- 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
- Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have fewer rejection events than patients who discontinue these drugs
Read more
Secondary Hypotheses:
- Patients who undergo elective nephrectomy (to remove the failed kidney transplant) will have fewer deaths than those who retain the failed kidney transplant
- 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
- 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
- Patients who undergo elective nephrectomy will have higher levels of allosensitization (anti-HLA antibodies) than patients who retain the failed kidney transplant
Read the 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.
- Keywords
- Dialysis, Renal Transplantation, Failure of allograft
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Failed Kidney Transplant | Adults ≥ 18 years, initiating chronic dialysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death
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.
Measured: 48 months
Sepsis
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.
Measured: 48 months
Rejection of failed allograft.
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.
Measured: 48 months
Allosensitization
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®.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2011 (estimated)
- Study startAug 2011
- Primary completionOct 2016
- Study completionJul 2017
Why it stopped: Funding ended.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Graft RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), St. Paul's Hospital, Canada, Vancouver General Hospital, Kingston Health Sciences Centre, University of Saskatchewan, University of Calgary, University of Manitoba, University Health Network, Toronto, Unity Health Toronto, St. Joseph's Healthcare Hamilton, London Health Sciences Centre, McGill University Health Centre/Research Institute of the McGill University Health Centre, Maisonneuve-Rosemont Hospital, Centre hospitalier de l'Université de Montréal (CHUM), CHU de Quebec-Universite Laval, University of Alberta
- Responsible party
- Sponsor
- Investigators
- Greg Knoll, MD, Principal investigator, U of Ottawa, The Ottawa Hospital, OHRIJohn Gill, MD, Principal investigator, UBC, St Paul's Hospital Vancouver, BC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01296061
- Sponsor's protocol ID
- CIHR FRN MOP-102732
- Status last verified
- Sep 2019
- First submitted
- 8 Feb 2011
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Immunosuppressive Medication Use on Patient Outcomes Following Kidney Transplantation Failure
- ClinicalTrials.gov ID
- NCT01296061
- Acronym / sponsor ID
- CIHR FRN MOP-102732
- Keywords
- Dialysis, Renal Transplantation, Failure of allograft
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Funding ended.
- Enrolment
- 270 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), St. Paul's Hospital, Canada, Vancouver General Hospital, Kingston Health Sciences Centre, University of Saskatchewan, University of Calgary, University of Manitoba, University Health Network, Toronto, Unity Health Toronto, St. Joseph's Healthcare Hamilton, London Health Sciences Centre, McGill University Health Centre/Research Institute of the McGill University Health Centre, Maisonneuve-Rosemont Hospital, Centre hospitalier de l'Université de Montréal (CHUM), CHU de Quebec-Universite Laval, University of Alberta
- Study start
- Aug 2011
- Primary completion
- Oct 2016 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 15 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Hypotheses:
- Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have more deaths than patients who discontinue these drugs
- 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
- 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:
- Patients who undergo elective nephrectomy (to remove the failed kidney transplant) will have fewer deaths than those who retain the failed kidney transplant
- 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
- 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
- Patients who undergo elective nephrectomy will have higher levels of allosensitization (anti-HLA antibodies) than patients who retain the failed kidney transplant
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Failed Kidney Transplant | – | –Adults ≥ 18 years, initiating chronic dialysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients ≥ 18 years, who initiate chronic dialysis treatment after failure of a first kidney transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Death
Time frame: 48 months
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
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
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
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®.
Results and safety
The study was stopped early (reason given: Funding ended.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Greg Knoll, MD principal investigator
U of Ottawa, The Ottawa Hospital, OHRI
John Gill, MD principal investigator
UBC, St Paul's Hospital Vancouver, BC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Graft Rejection and Renal Failure Chronic Requiring Dialysis, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: stopped early, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Funding ended.). Results are not available in the source record.
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?
Death (time frame: 48 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Sep 2019.