To evaluate the graft function of everolimus and reduced Calcineurin Inhibitor versus mycophenolic acid sodium and standard Calcineurin Inhibitor in adult renal transplant recipients.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2014/07/004772
• Date of registration: 25-07-2014
• Prospective Registration: No
• Primary sponsor: Novartis Healthcare Private Limited
• Public title: To evaluate the graft function of everolimus and reduced Calcineurin Inhibitor versus mycophenolic acid sodium and standard Calcineurin Inhibitor in adult renal transplant recipients.
• Scientific title: A 24 month, multicenter, randomized, open-label safety and efficacy study of concentration-controlled everolimus with reduced calcineurin inhibitor vs mycophenolate with standard calcineurin inhibitor in de novo renal transplantation- Advancing renal TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen.
• Date of first enrolment: 03-03-2014
• Target sample size: 1972
• Recruitment status: Open to Recruitment
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7669
• Study type: Interventional
• Study design: Randomized, Parallel Group Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Open Label
• Phase: Phase 4

Countries of recruitment

Belgium, Czech Republic, Egypt, Germany, India, Italy, Netherlands, Slovakia, South Africa, Spain, Switzerland

Contacts

• Name: Murugananthan K
• Affiliation: Head Clinical Development in Novartis Healthcare Private Limited

• Name: Murugananthan K
• Affiliation: Head Clinical Development in Novartis Healthcare Private Limited

Key inclusion & exclusion criteria

Inclusion criteria: 1.Written informed consent obtained.

2.Subject randomized within 24 hr of completion of transplant surgery.

3.Recipient of a kidney with a cold ischemia time < 30 hours.

4.Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.


Exclusion criteria: 1.Subject unable to tolerate oral medication at time of randomization.

2.Use of other investigational drugs at the time of enrollment.

3.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.

4.Multi-organ transplant recipient.

5.Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.

6.Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.

7.Subject who is HIV-positive.

8.HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels >= 2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable.

9.Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV).

10.Subject with a BMI greater than 35.

11.Subject with severe systemic infections, current or within the two weeks prior to randomization.

12.Subject requiring systemic anticoagulation.

13.History of malignancy of any organ system.

14.Subject with severe restrictive or obstructive pulmonary disorders.

15.Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled.

16.Subject with white blood cell (WBC) count <= 2,000 /mm3 or with platelet count <= 50,000 /mm3.

17.Pregnant or nursing (lactating) women.

18.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- â?¢End Stage Renal Disease (ESRD) â?¢Chronic Kidney Disease (CKD) â?¢Hemodialysis â?¢Renal Replacement Therapy â?¢Renal Transplantation

Intervention(s)

Intervention1: Everolimus and reduced calcineurin inhibitor: Everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) inhibitor. All subjects are to receive maintenance therapy with corticosteroids and induction therapy.[Total Duration is 24 months] [Route of administration is Oral][frequency of drug- daily]
Control Intervention1: Standard dose of CNI tacrolimus/cyclosporine) and Mycophenolate: Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus). All subjects are to receive maintenance therapy with corticosteroids and induction therapy.[Total Duration is 24 months] [Route of administration is Oral][frequency of drug- daily]

Primary Outcome(s)

Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR)less than 50 mL/min/1.73m2.

Timepoint: Month 12 is Primary,Month 24 secondary

Secondary Outcome(s)

1)Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death

2)Incidence of failure on the composite endpoint of tBPAR, graft loss, death or eGFR less than 50 mL/min/1.73m2

3)Incidence of failure on the composite endpoint of graft loss or death

4)Incidence of death, graft loss, tBPAR, BPAR, tAR, AR and humoral rejection.

Timepoint: 1)Time Frame: Month 12 and 24

2)Time Frame: Month 12 and 24

3)Time Frame: Month 12 and 24

4)Time Frame: Month 12 and 24

Secondary ID(s)

CRAD001A2433 dated 01-Jul-2013

NCT01950819

Source(s) of Monetary Support

Novartis Pharma AG, Basel, Switzerland.

Ethics review

Status: Approved
Approval date: 03/03/2014
Contact:

Institutional Ethics committee_Max Healthcare superspeciality Hospital

Status: Approved
Approval date: 09/05/2014
Contact:

Ethics Committee & Institutional Review Board (IRB)_christian Medical College

Status: Approved
Approval date: 27/06/2014
Contact:

Institutional Ethics Committee_Columbia Asia Referral Hospital

Status: Approved
Approval date: 07/10/2014
Contact:

clinical research Ethics Committee

Status: Not Approved
Approval date:
Contact:

Ethics Committee,Osmania Medical College