Clinical trial NCT00443508: Reduction or Discontinuation of CNI's With Conversion to Everolimus-Based Immunosuppresion
Official title: Reduction or Discontinuation of Calcineurine Inhibitors With Conversion to Everolimus-Based Immunosuppresion to Alleviate Chronic Allograft Nephropathy (CAN) in Kidney Transplant Recipients: A Prospective Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Kidney Diseases
Keywords: everolimus
renal transplant
tacrolimus
Certican
CHRONIC ALLOGRAFT NEPHROPATHY
Renal transplant patients
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2007-03-06
Enrollment: 60
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is design to compare two different strategies aiming to lessen the degree of the ongoing process of allograft injury either by removing tacrolimus from the maintenance immunosuppressive protocol or by reducing tacrolimus dose.

The primary goal is to assess the change in renal function at 6 and 12 months after conversion using creatinine levels and calculated creatinine clearance.

The study will include two groups: The study group of 30 patients and a matched control group with creatinine levels at similar range.

Detailed description: This study is design to compare two different strategies aiming to lessen the degree of the ongoing process of allograft injury either by removing tacrolimus from the maintenance immunosuppressive protocol or by reducing tacrolimus dose.

The primary goal is to assess the change in renal function at 6 and 12 months after conversion using creatinine levels and calculated creatinine clearance.

The study will include two groups: The study group of 30 patients and a matched control group with creatinine levels at similar range.

Patients will undergo the following baseline studies:

1. Doppler ultrasound to exclude any mechanical or a vascular problem.
2. A kidney biopsy to define the histological changes (degree of interstitial fibrosis, tubular and glomerular changes). The biopsies will be stained also for C4D and for fibrinogenic markers (TGF-beta, and collagen).
3. A 24-hour urine protein excretion and creatinine clearance
4. Echocardiography study
5. Carotid Ultrasound

The following parameters will be monitored every clinic visit throughout the study period:

1. SMA-12 including creatinine levels.
2. A complete blood count.
3. Cholesterol, HDL-cholesterol and triglyceride levels.
4. Blood pressure measurements (X2)
5. The number of blood pressure medications.
6. Cholesterol lowering medication requirement
7. Urine protein excretion (quantitative spot-test )
8. Protein amount in the urine

Study end points:

The data will be evaluated based on an intention to treat analysis and the following parameters will be compared between the two groups:

1. Creatinine levels and calculated creatinine clearance
2. Spot urine for Cr./protein ratio
3. 24-hr. protein excretion
4. Change in peak diastolic and mean arterial blood pressure
5. The number and dosage of blood pressure medications
6. Cholesterol, HDL and triglyceride levels
7. Proportion of patients on cholesterol lowering agents
8. Number and severity of biopsy proven acute rejection episodes
9. Incidence of biopsy proven chronic rejection. (depends on per protocol biopsy at end of study)
10. Patient and graft survival

Eligibility criteria: Inclusion Criteria:

* Patients on CNI FK \< 5 ng/m"l with MPA / Imuran with or without steroids
* Renal impairment GFR between 30 - 70 m"l/minute/
* Patient who signed Informed consent
* Patient with no contraindication to renal biopsy
* Women who are not pregnant and will use contraception

Exclusion Criteria:

* Proteinuria \> 100 m"g/mmol Creatinine
* Acute rejection during 3 months before screening
* WBC \< 2500, plt \< 50,000,
* Nephropathy due to polyoma virus
* Patients on other investigational drugs
* Patients on rapamycin
* Patients with HIV or other systemic infection
* Inability to comply with protocol requirements
* Active or history of malignancy

Primary outcomes:
measure: The primary goal is to assess the change in renal function
measure: at 6 and 12 months after conversion using creatinine levels
measure: and calculated creatinine clearance.
Secondary outcomes:
measure: The secondary aim is to assess changes in cardiovascular risks at
measure: 12 months after conversion (glucose control., cholesterol and
measure: triglyceride levels and hypertension control), incidence of
measure: acute and chronic rejection and graft and patient survival rates.
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Transplantation department, rabin Medical Center
Study officials:
affiliation: Rabin Medical Center, head of Transplantation department
name: Eytan Mor, Prof
role: PRINCIPAL_INVESTIGATOR
References: