Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection

NCT00707759 | Completed Phase 3 Results DMC

• 1 other identifier: Fondecyt1080166
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The present study investigates the safety and efficacy of steroid withdrawal at six days post-transplant in pediatric renal recipients under concomitant immunosuppression based on antibodies anti IL2 (interleukin 2), Tacrolimus (TAC) and Mycophenolate Mofetil (MMF). To investigate the impact of this protocol in growth, bone metabolism, insulin- sensitivity and evaluate the expression of IL17 (interleukin 17) and mRNA FOXP3 (messenger ribonucleic acid forkhead box protein 3) as early markers of acute rejection (blood, urine and renal biopsy). Hypothesis:Steroid withdrawal in renal pediatric transplant patients improves growth and bone metabolism without increasing the risk of acute rejection. The expression of FoxP3/IL17 in urine cells could be an early molecular markers of acute rejection.

Conditions

Kidney Diseases

Keywords

Pediatric renal transplantation,Bone metabolism (DXA-pQCT); mRNAFOXP3/IL-17,Steroid withdrawal

Outcome Measures

Primary Outcomes (1)

• Stimulation of Growth After 12 Months (Delta Z-score)

  12 months

Secondary Outcomes (1)

• Growth-factors (IGF-I, IGFBP-3) Bone Metabolism (FA, Ca/Cru, CaxP, 25(OH)VitD, FGF23, Klotho, PTH, DXA, pQCT) Insulin-sensitivity by ISI Method. Molecular Markers - Acute Rejection (FOXP3/IL-17). Acute Rejection Incidence/Protocol Renal Biopsy

  12 months

Study Arms (2)

A: withdrawal steroids

EXPERIMENTAL

Arms A: TAC + MMF + withdrawal steroids over a six-days following randomization. 1°day: Methylprednisolone iv, 2-3 mg/kg/d 3 doses 2ºday: Methylprednisolone iv, 2-3 mg/kg/d 3 doses 3°day: Prednisone 2 mg/kg/d in 2 doses 4ºday: Prednisone 1 mg/kg/d in 2 doses 5ºday: Prednisone 0.5 mg/kg/d in 2 doses 6ºday: Prednisone 0.25 mg/kg/d in 2 doses 7ºday: Stop Prednisone

Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone

B

ACTIVE COMPARATOR

Arms B: TAC + MMF + prednisolone (see schedule)/day 10°days after Tx: 2 mg/kg/d Day 11 - 20: 1 mg/kg/d Day 21 - 30: 0.5 mg/kg/d Day 31 - 60: 0.3 mg/k/d Week 8 - 12: 0.25 mg/k/d Week 12 - 16: 0.20 mg/k/d Week 16 - 20: 0.15 mg/k/d Month 6 - 12: 0.10 - 0.12 mg/k/d

Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone

Interventions

Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone DRUG

Arms A: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + withdrawal steroids over a six-days following randomization. 1°day: Methylprednisolone iv, 2-3 mg/kg/d 3 doses 2ºday: Methylprednisolone iv, 2-3 mg/kg/d 3 doses 3°day: Prednisone 2 mg/kg/d in 2 doses 4ºday: Prednisone 1 mg/kg/d in 2 doses 5ºday: Prednisone 0.5 mg/kg/d in 2 doses 6ºday: Prednisone 0.25 mg/kg/d in 2 doses 7ºday: Stop Prednisone

A: withdrawal steroids

Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone DRUG

Arms B: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone (see schedule)/day 10°days after Tx: 2 mg/kg/d Day 11 - 20: 1 mg/kg/d Day 21 - 30: 0.5 mg/kg/d Day 31 - 60: 0.3 mg/k/d Week 8 - 12: 0.25 mg/k/d Week 12 - 16: 0.20 mg/k/d Week 16 - 20: 0.15 mg/k/d Month 6 - 12: 0.10 - 0.12 mg/k/d

B

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age \< 16.0 years
• Bone age of boys \< 15 years, of girls \< 13 years
• Prepuberal Tanner Status I
• First or second kidney transplant, living or deceased kidney donation
• Immunosuppression with Tacrolimus (TAC),Mycophenolate mofetil (MMF)
• Patients and parents, respectively, have given their written consent after enlightenment (informed consent)

You may not qualify if:

• Irreversible rejection of former transplant
• Highly reactive (\> 30%) lymphocytotoxic antibodies within 12 months prior to transplantation
• Suspected insufficient medication compliance in dialysis
• Patients receiving a basic immunosuppression other than that prescribed in this protocol
• Simultaneous therapy with growth hormone after renal transplant

Sponsors & Collaborators

• Fondo Nacional de Desarrollo Científico y Tecnológico, Chile: lead

Study Sites (1)

Calvo Mackenna Children Hospital

Santiago, Metropolitan Region, Chile

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

Tacrolimus; Prednisolone

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Maria Angela Delucchi
• Organization: FONDECYT

madelucchi@gmail.com

56-2-25755972

Study Officials

• Maria Angela Delucchi, MD

  Calvo Mackenna Children´s Hospital-University of Chile

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: July 1, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2014
• Last Updated: November 10, 2015
• Results First Posted: November 10, 2015

Record last verified: 2015-10

Locations

CL (1)