Assessing DSA Formation, Diabetes, Viral Infections, Structural Kidney Changes With an Everolimus-based Regimen (ADVISE)

Kidney Failure Clinical Trial

— ADVISE  

Official title:

Exploring the Impact of de Novo Everolimus on Key Determinants of Long Term Outcome After Kidney Transplantation: NODAT, Viral Infection, DSA, Proteinuria and Graft Histology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02316938
• Other study ID #: CRAD001AAU13
• Status: Completed
• Phase: Phase 4
• Start date: February 22, 2015
• Est. completion date: December 18, 2017

Study information

• Verified date: October 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CRAD001AAU13 is a substudy of CRAD001A2433. The core study CRAD001A2433 is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating graft function with everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients. Patients in this study may use cyclosporine or tacrolimus as the CNI.

Description:

Patients enrolled in the core study CRAD001A2433 in Australia will be eligible for recruitment into CRAD001AAU13. These patients will undergo additional tests (including 4 kidney allograft biopsies) as part of the substudy that will be conducted during core study CRAD001A2433 visits. At Day 0 (day of transplant /TX), Month 2, Month 12 and Month 24 additional samples (serum, whole blood and kidney biopsy) will be taken for the purposes of this substudy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 18, 2017
• Est. primary completion date: December 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Currently randomized in study CRAD001A2433.

2. Written informed consent for CRAD001AAU13 must be obtained before any assessment is performed

Exclusion Criteria:

1. Patients for which the investigator believes performing protocol required biopsies will place the patient at unacceptable level of risk.

Related Conditions & MeSH terms

• Kidney Failure
• Renal Insufficiency
• Virus Diseases

Intervention

Drug:
• Everolimus and reduced CNI
MTORi inhibitor, given as part of the core CRAD001A2433 study.
• Calcineurin Inhibitor and MPA
Will either be cyclosporine or tacrolimus. Used as standard of care in this patient population, but at a lower dose in the everolimus arm and at a standard dose in the comparator arm. Treatment given as part of the core CRAD001A2433 stud.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Heidelberg Heights	Victoria
Australia	Novartis Investigative Site	Parkville,	Victoria
Australia	Novartis Investigative Site	Randwick	New South Wales
Australia	Novartis Investigative Site	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Structural kidney damage	Kidney allograft biopsies will be taken at baseline, months 2, 12 and 24 to assess the structural kidney damage using the BANFF 2013 criteria.; Development of structral allograft damage (Banff classification) over 24 months will be compared between treatment groups using modelling techniques that take into account the repeated measures, nature of the data and all available data.	Baseline to month 24.
Secondary	Incidence of de novo Donor specific antibodies formation	Serum blood samples analysed to assess presence and evolution of anti HLA donor specific antibodies.; The number and percentage of patients with anti HLA and donor specific antibodies at each study visit will be presented using a generalised linear mixed model framework as well as a Kaplan-Meier curve to portray the change over time.	Baseline to month 24
Secondary	Impaired glucose tolerance and new onset diabetes	Subjects' diabetes status is collected at baseline as part of medical history. At month 2, serum blood test taken pre glucose drink and 2 hours post glucose drink. Subjets classified based on the level of glucose as: No diabetes (fasting plasma glucose <6.1mmol/L or 2 hour OGTT <7.8mmol/L) Prediabetes (fasting plasma glucose 6.1-6.9mmol/L or 2hr OGTT 7.8-11mmol/L) Diabetes (fasting plasma glucose >/= 7.0mmol/L or 2hr OGTT >/= 11.1mmol/L) Shift tables will present the change in diabetes status between baseline and month 2. The odds of becoming diabetic by month 2 (new onset diabetes) will be compared using a generalised linear model, in particular logisitc regression.	Month 2
Secondary	Correlation between HbA1c and oral glucose tolerance test	Serum blood samples are taken pre and post glucose drink at month 2. Results are produced for plasma glucose levels and HbA1c in mmol/L. Correlation between the results will be investigated using a generalised linear model.	Month 2
Secondary	Development of biochemical markers of viral infections	Blood samples are analysed at baseline months 2, 12 and 24. The following viral loads are measured in copies per ml: CMV (Cytomegalo virus) via PCR BK viremia via RT-PCR EBV (Epstein Barr Virus) via PCR Descriptive staistics will be presented for the viral load of each of the biochemical markers at each timepoint.	Baseline - month 24