Clinical trial NCT01056822: Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.
Official title: Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prophilaxis of Acute Rejection in Patients Receiving a Renal Allograft
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-01-26
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.


Eligibility criteria: Inclusion criteria

1. Renal transplant recipients ≥ 1 year and ≤ 5 years prior1 to inclusion in the study.
2. Patients who were receiving an immunosuppressive regimen including MMF ≤1000 mg/day and ≥ 250 mg/day 4 and Prograf®1 or Advagraf®6 (levels ≥7 ng/ml).
3. Patients who had been receiving the current maintenance immunosuppressive regimen with stable doses of MMF for at least the past 3 months.2
4. Patients included must have had Prograf® or Advagraf® levels ≥ 7ng/ml4 for at least one month prior to inclusion in the trial.2
5. Patients with low immunological risk, in the investigator's opinion.
6. Patients with an estimated glomerular filtration rate based on the MDRD formula of \> 30 ml/min x 1.73 m2.1
7. Patients over 18 years of age.1
8. Patients who were able to understand the study information and give written informed consent.
9. Patients who were able to meet all study requirements, including completing questionnaires and attending study visits.

Exclusion criteria

1. Patients with GI symptoms known or assumed not to be caused by mycophenolic acid (MPA) treatment (e.g. oral bisphosphonate-induced infectious diarrhoea).
2. Patients with chronic inflammatory bowel disease.
3. Diabetic patients.
4. Acute rejection \< 1 month prior to inclusion in the study.
5. Patients with leukopenia (\< 3500 cells/mm3) or thrombocytopenia (\< 100,000 cells/mm3).
6. Women of childbearing potential who were planning to become pregnant, were pregnant and/or breastfeeding, or who did not wish to use effective contraception \[hormonal contraceptives (implantation, patches, oral) and double-barrier methods (any double combination of: IUD, male or female condoms with spermicidal gel, diaphragm, contraceptive sponge, cervical cap)\].
7. Presence of psychiatric illness (such as schizophrenia, major depression) that, in the investigator's opinion, could interfere with study requirements.
8. Patients who were undergoing surgery for an acute condition or who were hospitalised.
9. Any other medical condition that, in the investigator's opinion based on blood counts or chart review, could interfere with completion of the study, including but not limited to visual problems or cognitive impairment.
10. Patients who were receiving or had received any investigational medicinal product during the 30 days prior to inclusion in the study.

Primary outcomes:
measure: Number of Participants Achieving at Least Two Mycophenolic Acid (MPA) Dose Steps Higher and Reducing Tacrolimus Dose at the End of the Study
timeFrame: at 12 months from baseline
measure: Number of Participants That Achieved One Dose Step Higher With Mycophenolic Acid (MPA) or Mycophenolate Mofetil (MMF), According to the Treatment Group Assigned at the End of the Study (Final Visit) Compared to Baseline Dose
timeFrame: at 12 months from baseline
measure: Participants With Reduction in Tacrolimus or Tacrolimus Extended Release Levels at the End of the Study (Final Visit) Compared to Baseline Dose.
timeFrame: at 12 months from baseline
measure: Mean Mycophenolic Acid (MPA) Doses at the End of the Study (Final Visit) Compared to Baseline Dose.
timeFrame: at 12 months from baseline
Secondary outcomes:
measure: Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
timeFrame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)
measure: Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
timeFrame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)
measure: Gastrointestinal Symptom Rating Scale (GSRS) Item Score
timeFrame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)
measure: Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
timeFrame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)
measure: Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score.
timeFrame: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)
measure: Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
timeFrame: at 12 months from baseline
measure: Duration of Exposure to the Study Medicinal Product, Mycophenolate Sodium Descriptive Statistics. Safety Population Per Treatment Group
timeFrame: at 12 months from baseline
measure: Dose of the Study Medicinal Product Mycophenolate Sodium (MPS)
timeFrame: at 12 months from baseline
measure: Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF)
timeFrame: at 12 months from baseline
Other outcomes:
Locations:
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Toledo
country: Spain
facility: Novartis Investigative Site
state: Castilla la Mancha
city: Valladolid
country: Spain
facility: Novartis Investigative Site
state: Castilla y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Palma de Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Las Palmas de Gran Canaria
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Barakaldo
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: