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

NCT01046045 | Completed Phase 4

• 1 other identifier: CRE-2008.004-T
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Chronic Allograft Dysfunction in Renal Transplantation

Keywords

mammalian target-of-rapamycin inhibitors; chronic allograft dysfunction; everolimus; calcineurin inhibitors

Outcome Measures

Primary Outcomes (1)

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

  12 months

Secondary Outcomes (3)

• estimated glomerular filtration rate at 12 months

  12 months

• morphometric studies

  12 months

• cytokines before and after everolimus conversion

  12 months

Study Arms (2)

Everolimus

ACTIVE COMPARATOR

before and after everolimus; in other words, comparison of specified outcome before and after treatment with everolimus

Drug: everolimus

Calcineurin-inhibitor immunosuppression

ACTIVE COMPARATOR

Cyclosporin-based immunosuppression without everolimus

Drug: everolimus

Interventions

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

Also known as: Certican

Calcineurin-inhibitor immunosuppression; Everolimus

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Kai Ming Chow, MBChB

  Chinese University of Hong Kong, Prince of Wales Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Consultant

Study Record Dates

• First Submitted: January 6, 2010
• First Posted: January 11, 2010
• Study Start: April 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: June 1, 2013
• Last Updated: June 22, 2015

Record last verified: 2015-06

Locations

HK (1)