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A Prospective Study to Investigate Mycophenolic Acid (MPA) Exposure Through Area Under the Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) and After Conversion to Mycophenolate Sodium (EC-MPS) (AUC-MPA)

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ClinicalTrials.gov Identifier: NCT01822483
Recruitment Status : Completed
First Posted : April 2, 2013
Last Update Posted : April 3, 2015
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Valter Duro Garcia, Irmandade Santa Casa de Misericórdia de Porto Alegre

Tracking Information
First Submitted Date  ICMJE March 21, 2013
First Posted Date  ICMJE April 2, 2013
Last Update Posted Date April 3, 2015
Study Start Date  ICMJE April 2013
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2013)
Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1). [ Time Frame: Baseline ]
Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2013)
  • Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA); [ Time Frame: Baseline; month 6. ]
    Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA);
  • Evaluate the interaction between MMF or EC-MPS and the proton pump inhibitor omeprazole through the AUC in patients with MPA below target level (30mcg*h ml-1). [ Time Frame: 6 months ]
    Evaluate the interaction between MMF or EC-MPS and the proton pump inhibitor omeprazole through the AUC in patients with MPA below target level (30mcg*h ml-1).
  • Evaluate the association of MPA AUC with renal function estimated by MDRD formula. [ Time Frame: Baseline; day one; months 2, 4 and 6. ]
    Evaluate the association of MPA AUC with renal function estimated by MDRD formula.
  • Evaluate the MPA_AUC in renal transplant patients converted to mycophenolate sodium (MPS) with equivalent dose of mycophenolate mofetil (MMF). [ Time Frame: Baseline, five days after day one, fourteen days after day one, months 2,4 and 6 ]
    Evaluate the MPA_AUC in renal transplant patients who were taking mycophenolate mofetil (MMF) and were converted to the use of mycophenolate sodium (MPS) by having the MPA concentration below the target level of 30 mcg*h ml-1.
  • Evaluate the MPA_AUC in renal transplant patients maintained with mycophenolate mofetil (MMF). [ Time Frame: baseline, months 2,4 and 6 ]
    Evaluate the AUC_MPA in renal transplant patients maintained with mycophenolate mofetil(MMF) by having the MPA concentration between 30-60 mcg*h ml-1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Prospective Study to Investigate Mycophenolic Acid (MPA) Exposure Through Area Under the Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) and After Conversion to Mycophenolate Sodium (EC-MPS)
Official Title  ICMJE A Prospective Study to Investigate Mycophenolic Acid (MPA) Exposure Through Area Under the Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) and After Conversion to Mycophenolate Sodium (EC-MPS)
Brief Summary The purpose of this study is investigate mycophenolic acid exposure through area under the curve in renal transplants recipients treated with mycophenolate mofetil and after conversion to mycophenolate sodium.
Detailed Description

A growing body of evidence has shown that mycophenolate acid (MPA) exposure assessment and dosage adjustment are necessary in patients treated with mycophenolate mofetil (MMF), but there is still limited information about the dose-exposure-effect relationship of the enteric-coated mycophenolate sodium (EC-MPS) formulation that has quite different physicochemical properties (TETT et al., 2011).

Pharmacokinetically guided exposure-controlled area under the concentration-time curve (AUC) approaches are helpful to limit interpatient variability of MPA exposure and to improve the clinical outcome of organ transplant recipients (TETT et al., 2011).

MPA area under the concentration-time curve values between 30 and 60 μg h/mL in the early post-transplant period reduces the risk of acute rejections and seems to be appropriate in renal allograft recipients taking mycophenolate sodium (MPS) and calcineurin inhibitors (GRINYÓ et al., 2009; SOMMERER et al., 2010).

Among the benefits of therapeutic drug monitoring of MPA are the evaluation of interaction between MPA and proton pump inhibitors and association of donor-specific antibodies reduction.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Renal Transplantation
Intervention  ICMJE
  • Drug: Mycophenolate sodium
    The conversion will be performed abruptly for all patients. Mycophenolate mofetil will be discontinued one day before the day of conversion (Day 1). Mycophenolate sodium will be introduced on day 1 with equivalent doses.
  • Drug: Mycophenolate mofetil
    Mycophenolate mofetil dose will be maintained or adjusted to keep 30 to 60 mg*h ml-1.
Study Arms  ICMJE
  • Experimental: Mycophenolate sodium
    Arm1(Conversion):MPA AUC below 30mcg*h ml-1 - MPS+Calcineurin inhibitor+prednisone
    Intervention: Drug: Mycophenolate sodium
  • Active Comparator: Mycophenolate mofetil
    Arm2(Maintained):MPA AUC between 30 to 60 mg*h ml-1 or above 60 mg - MMF+Calcineurin inhibitor+prednisone
    Intervention: Drug: Mycophenolate mofetil
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2013)
100
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years at the time of screening;
  • Subjects above the sixth month post renal transplant;
  • Subjects receiving mycophenolate mofetil;
  • Women of childbearing potential (CBP) with a negative pregnancy test at screening (urine or serum);
  • Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study.

Exclusion Criteria:

  • Subjects who, in the opinion of the investigator, are not able to complete the study;
  • Recipients of multiple organ transplant (i.e., prior or concurrent transplantation of a non-renal allograft;
  • Use of any investigational drug or treatment up to 4 weeks before enrollment;
  • Subjects with a calculated GFR < 30ml/min (abbreviated MDRD formula);
  • Subjects with a screening total white blood cell count (WBC) ≤ 2000/mm3, hemoglobin ≤ 10g/dL and platelet count ≤ 100000/mm3;
  • TGO/AST, TGP/ALT and bilirubin with values three times higher that reference values;
  • History of malignancy within 3 years enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin;
  • Subjects who are known to be human immunodeficiency virus (HIV), hepatitis B or hepatitis C;
  • Chronic hepatic failure;
  • Planned treatment with immunosuppressive therapies other than those described in the protocol;
  • Recipients who required desensitization protocols.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01822483
Other Study ID Numbers  ICMJE CERL080
CERL080ABR08T ( Other Identifier: NOVARTIS )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Valter Duro Garcia, Irmandade Santa Casa de Misericórdia de Porto Alegre
Study Sponsor  ICMJE Irmandade Santa Casa de Misericórdia de Porto Alegre
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Valter Garcia, Physician IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
Study Chair: Elizete Keitel, Physician IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
Study Chair: Daniela Seelig, Physician IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE
Study Chair: Fabiano Klaus, Physician IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE
Study Director: Ronivan Dal Pra, Pharmacist IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
Study Director: Larissa Pacheco, Pharmacist IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
Study Director: Bruna Cardoso, Pharmacist IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
Study Director: Roger Kist, Trainee IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
Study Director: Helen Zanetti, Pharmacist IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE
PRS Account Irmandade Santa Casa de Misericórdia de Porto Alegre
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP