Completed

NCT Number: NCT01046045

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.

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Key information

Conditions

Chronic Allograft Dysfunction in Renal Transplantation

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Prince of Wales Hospital

Hong Kong

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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
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

Treatment and study plan

Everolimus

Drug

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

Other names: Certican

Primary outcomes

change in glomerular filtration rate decline rate and histological degree of fibrosis before and after treatment with everolimus

Time frame: 12 months

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

Sponsors and collaborators

Lead sponsor

Chinese University of Hong Kong

Other

Registry information

Official study title

Impact and Efficacy of Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients

Important dates

Study start: 2008
Primary completion: 2011
Study completion: 2013
First posted: Jan 11, 2010
Registry last updated: Jun 22, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.