Chronic Allograft Dysfunction in Renal TransplantationPhase 4NCT01046045
Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients
A Phase 4 study testing everolimus in people with Chronic Allograft Dysfunction in Renal Transplantation, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Despite the remarkable improvement in short-term patient and graft survival among the recipients of kidney transplants, the progressive renal dysfunction (chronic allograft dysfunction) accompanied by chronic interstitial fibrosis, tubular atrophy, vascular occlusive changes and glomerulosclerosis remains the chief… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Allograft Dysfunction in Renal Transplantation
- What is being tested?
- everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteHong Kong
- Study dates
- Apr 2008to Jun 2013
- Phase
- Phase 4
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-65 years
- Biopsy-confirmed chronic allograft dysfunction or chronic allograft nephropathy, in the absence of acute rejection episode within the preceding 2 months
- Proteinuria < 0.8 g/day (or spot urine protein < 0.8 g/g-Cr) in 2 consecutive samples within 8 weeks
- Serum creatinine < 220 μmol/L or estimated glomerular filtration rate > 40 ml/min/1.73m2 by the Nankivell formula, which had been validated in kidney transplant recipients; this equation was expressed for use with a standard serum creatinine assay: glomerular filtration rate = 6.7/(standardized serum creatinine in μmol/L / 1000) + weight (kg)/4 - urea (mmol/L)/2 - 100 / height2 (m) + 35 if the subject is male (or 25 if the subject is female)
- Willingness to give written consent and comply with the study protocol
Who cannot join
- Pregnancy, lactating or childbearing potential without effective method of birth control
- Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication
- Serum cholesterol > 7.8 mmol/L and/or serum triglycerides > 4.5 mmol/L despite lipid-lowering agents before conversion
- Systemic infection requiring therapy at study entry
- Participation in any previous trial on everolimus or sirolimus
- Patients receiving treatment of sirolimus or everolimus for other medical reasons within the past 12 months
Show all 11Show fewer
- On other investigational drugs within last 30 days
- History of a psychological illness or condition such as to interfere with the patient's ability to understand the requirement of the study
- History of non-compliance
- Chronic lung disease
- Known history of sensitivity or allergy to everolimus
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact and Efficacy of Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients
Despite the remarkable improvement in short-term patient and graft survival among the recipients of kidney transplants, the progressive renal dysfunction (chronic allograft dysfunction) accompanied by chronic interstitial fibrosis, tubular atrophy, vascular occlusive changes and glomerulosclerosis remains the chief cause of graft loss. As a result of this damage from immunologic and non-immunologic injury, the long-term survival of kidney transplants has changed little during the past decade. And, among the non-immunologic factors, calcineurin inhibitor nephrotoxicity has been shown to be the most common factor leading to long-term graft damage and progression to graft failure. This is further supported by the previous finding that long-term use of calcineurin inhibitor-based therapy leads to deterioration in kidney function, even in recipients of non-renal organ transplants.
The growing interest in calcineurin inhibitor minimisation protocols to optimize renal transplant outcome offers a new therapeutic options in the management of patients with chronic allograft dysfunction. Recently, mammalian target-of-rapamycin inhibitors (mTOR inhibitors) including everolimus has been shown to achieve an improvement of long-term function through an early modulation of immunosuppressive regimen. In this aspect, percutaneous renal graft biopsy represents an important diagnostic tool to allow visualization of the lesions of chronic allograft dysfunction and therefore the ability to delineate the potential improvement after introduction of everolimus. Histologic and morphometric findings from a protocol-mandated biopsies obtained from renal transplant recipients who are suffering from chronic allograft dysfunction and treated with everolimus are needed to provide a clinical blueprint for the drug's efficacy, if confirmed.
Read the detailed description
The objective of the present study is to evaluate the a priori hypothesis that calcineurin inhibitor and rescue immunosuppression with everolimus-based therapy would attenuate the renal parenchymal injury associated with long-term use of calcineurin inhibitors in renal transplant recipients with declining kidney function. Another objective of this study is to elucidate the efficacy of our approach to arrest the progression of allograft dysfunction by means of protocol renal allograft biopsy.
- Being tested
- everolimus
- Keywords
- mammalian target-of-rapamycin inhibitors, chronic allograft dysfunction, everolimus, calcineurin inhibitors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called Certican
everolimus at an initial daily loading dose between 1 and 4 mg dose of everolimus will be adjusted to maintain a trough everolimus level between 5 and 12 ng/mL
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Active comparator | before and after everolimus; in other words, comparison of specified outcome before and after treatment with everolimus Receives: Drug: everolimus |
| Calcineurin-inhibitor immunosuppression | Active comparator | Cyclosporin-based immunosuppression without everolimus Receives: Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in glomerular filtration rate decline rate and histological degree of fibrosis before and after treatment with everolimus
Measured: 12 months
Secondary outcomes (3)
estimated glomerular filtration rate at 12 months
Measured: 12 months
morphometric studies
Measured: 12 months
cytokines before and after everolimus conversion
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2010 (estimated)
- Study startApr 2008
- Primary completionNov 2011
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Allograft Dysfunction in Renal TransplantationStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chow Kai Ming, Chinese University of Hong Kong
- Investigators
- Kai Ming Chow, MBChB, Principal investigator, Chinese University of Hong Kong, Prince of Wales Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01046045
- Sponsor's protocol ID
- CRE-2008.004-T
- Status last verified
- Jun 2015
- First submitted
- 6 Jan 2010
- Last updated
- 22 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact and Efficacy of Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT01046045
- Acronym / sponsor ID
- CRE-2008.004-T
- Keywords
- mammalian target-of-rapamycin inhibitors, chronic allograft dysfunction, everolimus, calcineurin inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Nov 2011 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 11 Jan 2010 (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.
Despite the remarkable improvement in short-term patient and graft survival among the recipients of kidney transplants, the progressive renal dysfunction (chronic allograft dysfunction) accompanied by chronic interstitial fibrosis, tubular atrophy, vascular occlusive changes and glomerulosclerosis remains the chief cause of graft loss. As a result of this damage from immunologic and non-immunologic injury, the long-term survival of kidney transplants has changed little during the past decade. And, among the non-immunologic factors, calcineurin inhibitor nephrotoxicity has been shown to be the most common factor leading to long-term graft damage and progression to graft failure. This is further supported by the previous finding that long-term use of calcineurin inhibitor-based therapy leads to deterioration in kidney function, even in recipients of non-renal organ transplants.
The growing interest in calcineurin inhibitor minimisation protocols to optimize renal transplant outcome offers a new therapeutic options in the management of patients with chronic allograft dysfunction. Recently, mammalian target-of-rapamycin inhibitors (mTOR inhibitors) including everolimus has been shown to achieve an improvement of long-term function through an early modulation of immunosuppressive regimen. In this aspect, percutaneous renal graft biopsy represents an important diagnostic tool to allow visualization of the lesions of chronic allograft dysfunction and therefore the ability to delineate the potential improvement after introduction of everolimus. Histologic and morphometric findings from a protocol-mandated biopsies obtained from renal transplant recipients who are suffering from chronic allograft dysfunction and treated with everolimus are needed to provide a clinical blueprint for the drug's efficacy, if confirmed.
Detailed description
The objective of the present study is to evaluate the a priori hypothesis that calcineurin inhibitor and rescue immunosuppression with everolimus-based therapy would attenuate the renal parenchymal injury associated with long-term use of calcineurin inhibitors in renal transplant recipients with declining kidney function. Another objective of this study is to elucidate the efficacy of our approach to arrest the progression of allograft dysfunction by means of protocol renal allograft biopsy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Active comparator | Drug: everolimusbefore and after everolimus; in other words, comparison of specified outcome before and after treatment with everolimus |
| Calcineurin-inhibitor immunosuppression | Active comparator | Drug: everolimusCyclosporin-based immunosuppression without everolimus |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18-65 years
- Biopsy-confirmed chronic allograft dysfunction or chronic allograft nephropathy, in the absence of acute rejection episode within the preceding 2 months
- Proteinuria < 0.8 g/day (or spot urine protein < 0.8 g/g-Cr) in 2 consecutive samples within 8 weeks
- Serum creatinine < 220 μmol/L or estimated glomerular filtration rate > 40 ml/min/1.73m2 by the Nankivell formula, which had been validated in kidney transplant recipients; this equation was expressed for use with a standard serum creatinine assay: glomerular filtration rate = 6.7/(standardized serum creatinine in μmol/L / 1000) + weight (kg)/4 - urea (mmol/L)/2 - 100 / height2 (m) + 35 if the subject is male (or 25 if the subject is female)
- Willingness to give written consent and comply with the study protocol
Key exclusion criteria (11 listed)
- Pregnancy, lactating or childbearing potential without effective method of birth control
- Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication
- Serum cholesterol > 7.8 mmol/L and/or serum triglycerides > 4.5 mmol/L despite lipid-lowering agents before conversion
- Systemic infection requiring therapy at study entry
- Participation in any previous trial on everolimus or sirolimus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: Certicaneverolimus at an initial daily loading dose between 1 and 4 mg dose of everolimus will be adjusted to maintain a trough everolimus level between 5 and 12 ng/mL | Drug | Calcineurin-inhibitor immunosuppression, Everolimus |
Primary outcome
change in glomerular filtration rate decline rate and histological degree of fibrosis before and after treatment with everolimus
Time frame: 12 months
3 secondary outcomes
estimated glomerular filtration rate at 12 months
Time frame: 12 months
morphometric studies
Time frame: 12 months
cytokines before and after everolimus conversion
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2015.
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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.
Kai Ming Chow, MBChB principal investigator
Chinese University of Hong Kong, Prince of Wales Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing everolimus in people with Chronic Allograft Dysfunction in Renal Transplantation, run by Chinese University of Hong Kong at 1 site in Hong Kong.
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 5 inclusion and 11 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 22 Jun 2015. 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 Hong Kong. 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
change in glomerular filtration rate decline rate and histological degree of fibrosis before and after treatment with everolimus (time frame: 12 months). 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 22 Jun 2015.