Liver TransplantationPhase 4NCT00545402

A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.

A Phase 4 study testing Mycophenolate mofetil, adjusted dose, Tacrolimus and Corticosteroids, IV in people with Liver Transplantation, run by Hoffmann-La Roche at 16 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Liver Transplantation
What is being tested?: Mycophenolate mofetil, adjusted dose, Tacrolimus and Corticosteroids, IV
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 180 participants
Where: 16 sitesFrance
Study dates: Nov 2007to Jul 2011
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

adult patients, >=18 years of age;
recipient of a first orthotopic liver transplant.

Who cannot join

history of organ transplants;
patient receiving a multi-organ transplant;
calculated creatinine clearance <=30mL/min before transplant;
leukocyte count < 2000/mm3 at randomization;
history of cancer within past 5 years, except for successfully treated basal cell or squamous cell cancer, or in situ cervical cancer;
pregnant or breast-feeding females, or females of childbearing age not using effective contraception.

Trial locations and contacts

16 sites in 1 country.

City, postcode or hospital

16 sites in 1 country

France16 sites

Study site
Besançon, 25030
Study site
Bordeaux, 33076
Study site
Caen, 14033
Study site
Clichy, 92118
Study site
Créteil, 94010
Study site
Grenoble, 38043
Study site
Lille, 59037
Study site
Lyon, 69317
Study site
Lyon, 69437
Study site
Marseille, 13385
Study site
Montpellier, 34295
Study site
Nice, 06202
Study site
Paris, 75679
Study site
Rennes, 35033
Study site
Toulouse, 31059
Study site
Villejuif, 94804

Other trials in France

About this study

Official title: A Randomized, Open Label Study Comparing the Effect of CellCept With Therapeutic Drug Monitoring, Tacrolimus and a Corticosteroid-sparing Regimen Versus Fixed Dose CellCept, Tacrolimus and Corticosteroids Maintained up to 6 Months, on Acute Rejection and Safety in Liver Transplant Patients.

This 2 arm study will compare the efficacy and safety of two CellCept-containing treatment regimens in de novo liver transplant patients. Patients will be randomized into one of two groups, to receive either CellCept (at a starting dose of 3g/day po, adjusted according to exposure) standard dose tacrolimus and corticosteroids (10-15 mg/kg i.v. on day 0), or fixed dose CellCept 2g/day po, standard dose tacrolimus and corticosteroids (10-15mg/kg i.v. on day 0, then reducing from 20mg to 5mg over 6 months, and discontinuing after 6 months). The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Conditions: Liver Transplantation
Being tested: Mycophenolate mofetil, adjusted dose, Tacrolimus, Corticosteroids, IV, Mycophenolate mofetil, Standard dose, Corticosteroids, PO

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Mycophenolate mofetil, adjusted doseDrug
Also called CellCept
3 g/d PO BID during meals from Day 0 to Day 4, followed by dose adjustment based on AUC using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12.
TacrolimusDrug
Target trough level of 8-2 ng/mL from Day 0 to Month 1, adjusted to a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12
Corticosteroids, IVDrug
Also called Solu-Medrol
10-15 mg/kg IV pre-operation on Day 0
Mycophenolate mofetil, Standard doseDrug
Also called CellCept
2 g/d PO BID during meals from Day 0 to Month 12
Corticosteroids, PODrug
Also called Cortancyl
20 mg/d QDS from Day 0 through Month 1; 15 mg/day, TID from the end of Month 1 through Month 2; 10 mg/d BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.

Study groups in NCT00545402
Study group	Role	What they receive
MMF, Adjusted Dose; Tacrolimus; Corticosteroids	Experimental	Participants received mycophenolate mofetil (MMF) 3 grams per day (g/d), orally (PO), twice per day (BID) with meals from Day 0 to Day 4; the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12. Participants also received tacrolimus adjusted to a target trough level of 8 to (-) 12 nanograms per milliliter (ng/mL) from Day 0 to Month 1; the dose was adjusted to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 milligrams per kilogram (mg/kg), intravenously (IV), pre-operation on Day 0. Receives: Drug: Mycophenolate mofetil, adjusted dose; Drug: Tacrolimus; Drug: Corticosteroids, IV
MMF, Standard Dose; Tacrolimus; Corticosteroids	Active comparator	Participants received MMF 2 g/d, PO, BID with meals from Day 0 to Month 12. Participants also received tacrolimus adjusted to a target trough level of 8-12 ng/mL from Day 0 to Month 1; the dose was reduced to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 mg/kg, IV, pre-operation on Day 0; followed by 20 mg/d, PO, 4 times per day (QDS) from Day 0 through Month 1; 15 mg/d, PO, 3 times per day (TID) from the end of Month 1 through Month 2; 10 mg/d, PO, BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6. Receives: Drug: Tacrolimus; Drug: Corticosteroids, IV; Drug: Mycophenolate mofetil, Standard dose; Drug: Corticosteroids, PO

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant
Banff criteria required at least 2 of the 3 following features for a histopathological diagnosis of acute rejection: portal inflammation, bile duct inflammation, and venous endothelial inflammation. Each item was graded from 0 to 3 where 0 equals (=) mild, 2 = moderate, and 3 = severe. The sum of the 3 individual scores, from 0 to 9, corresponded to the Rejection Activity Index (RAI). If RAI = 0, 1, or 2, there was no evidence of rejection. If RAI = 3, there was borderline acute rejection. If RAI = 4 or 5, there was mild acute rejection. If RAI = 6 or 7, there was moderate acute rejection. If RAI = 8 or 9, there was severe acute rejection.
Measured: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment

Secondary outcomes (5)

Percentage of Participants With Graft Loss
Graft survival was defined as the time between the randomization date and the graft loss date. Participants were censored at the date of last follow up, the date of last contact or premature withdrawal, and date of death.
Measured: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.
Graft Survival
The median time, in months, between randomization and graft loss event. Participants were censored at the date of last follow up, the date of last contact or premature withdrawal, and date of death.
Measured: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.
Overall Survival (OS) at Month 12 - Percentage of Participants With an Event
OS was defined as the time between the date of randomization and death up to Month 12. Participants were censored at the date of last follow up and the date of last contact or premature withdrawal.
Measured: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12
Overall Survival at Month 12
The median time, in months, between randomization and OS event. Participants were censored at the date of last follow up and the date of last contact or premature withdrawal.
Measured: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12
Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review
The percentage of participants with biopsies of grafts evaluated by central review and scored according to Banff criteria at Month 12 post-transplant.
Measured: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2007Jul 2011

First posted17 Oct 2007 (estimated)
Study startNov 2007
Primary completionJul 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Liver TransplantationStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 180 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00545402
Sponsor's protocol ID: ML21273
Status last verified: Jun 2014
First submitted: 16 Oct 2007
Last updated: 14 Jul 2014
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open Label Study Comparing the Effect of CellCept With Therapeutic Drug Monitoring, Tacrolimus and a Corticosteroid-sparing Regimen Versus Fixed Dose CellCept, Tacrolimus and Corticosteroids Maintained up to 6 Months, on Acute Rejection and Safety in Liver Transplant Patients.
ClinicalTrials.gov ID: NCT00545402
Acronym / sponsor ID: ML21273
Conditions: Liver Transplantation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 180 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: Nov 2007
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 17 Oct 2007 (estimated)
Results: Posted 14 Jul 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
MMF, Adjusted Dose; Tacrolimus; Corticosteroids	Experimental	Drug: Mycophenolate mofetil, adjusted dose, Drug: Tacrolimus, Drug: Corticosteroids, IVParticipants received mycophenolate mofetil (MMF) 3 grams per day (g/d), orally (PO), twice per day (BID) with meals from Day 0 to Day 4; the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12. Participants also received tacrolimus adjusted to a target trough level of 8 to (-) 12 nanograms per milliliter (ng/mL) from Day 0 to Month 1; the dose was adjusted to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 milligrams per kilogram (mg/kg), intravenously (IV), pre-operation on Day 0.
MMF, Standard Dose; Tacrolimus; Corticosteroids	Active comparator	Drug: Tacrolimus, Drug: Corticosteroids, IV, Drug: Mycophenolate mofetil, Standard dose, Drug: Corticosteroids, POParticipants received MMF 2 g/d, PO, BID with meals from Day 0 to Month 12. Participants also received tacrolimus adjusted to a target trough level of 8-12 ng/mL from Day 0 to Month 1; the dose was reduced to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 mg/kg, IV, pre-operation on Day 0; followed by 20 mg/d, PO, 4 times per day (QDS) from Day 0 through Month 1; 15 mg/d, PO, 3 times per day (TID) from the end of Month 1 through Month 2; 10 mg/d, PO, BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

adult patients, >=18 years of age;
recipient of a first orthotopic liver transplant.

Key exclusion criteria (6 listed)

history of organ transplants;
patient receiving a multi-organ transplant;
calculated creatinine clearance <=30mL/min before transplant;
leukocyte count < 2000/mm3 at randomization;
history of cancer within past 5 years, except for successfully treated basal cell or squamous cell cancer, or in situ cervical cancer;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Mycophenolate mofetil, adjusted doseAlso: CellCept3 g/d PO BID during meals from Day 0 to Day 4, followed by dose adjustment based on AUC using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12.	Drug	MMF, Adjusted Dose; Tacrolimus; Corticosteroids
TacrolimusTarget trough level of 8-2 ng/mL from Day 0 to Month 1, adjusted to a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12	Drug	MMF, Adjusted Dose; Tacrolimus; Corticosteroids, MMF, Standard Dose; Tacrolimus; Corticosteroids
Corticosteroids, IVAlso: Solu-Medrol10-15 mg/kg IV pre-operation on Day 0	Drug	MMF, Adjusted Dose; Tacrolimus; Corticosteroids, MMF, Standard Dose; Tacrolimus; Corticosteroids
Mycophenolate mofetil, Standard doseAlso: CellCept2 g/d PO BID during meals from Day 0 to Month 12	Drug	MMF, Standard Dose; Tacrolimus; Corticosteroids
Corticosteroids, POAlso: Cortancyl20 mg/d QDS from Day 0 through Month 1; 15 mg/day, TID from the end of Month 1 through Month 2; 10 mg/d BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.	Drug	MMF, Standard Dose; Tacrolimus; Corticosteroids

Primary outcome

Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant
Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment
Banff criteria required at least 2 of the 3 following features for a histopathological diagnosis of acute rejection: portal inflammation, bile duct inflammation, and venous endothelial inflammation. Each item was graded from 0 to 3 where 0 equals (=) mild, 2 = moderate, and 3 = severe. The sum of the 3 individual scores, from 0 to 9, corresponded to the Rejection Activity Index (RAI). If RAI = 0, 1, or 2, there was no evidence of rejection. If RAI = 3, there was borderline acute rejection. If RAI = 4 or 5, there was mild acute rejection. If RAI = 6 or 7, there was moderate acute rejection. If RAI = 8 or 9, there was severe acute rejection.

5 secondary outcomes

Percentage of Participants With Graft Loss
Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.
Graft Survival
Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.
Overall Survival (OS) at Month 12 - Percentage of Participants With an Event
Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12
Overall Survival at Month 12
Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12
Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review
Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12

Results and safety

Results posted to the registry on 14 Jul 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Adjusted Mycophenolate Mofetil (MMF)+Tacrolimus+Corticosteroid	90	56
Fixed-Dose MMF + Tacrolimus + Corticosteroid (CS)	90	61

Primary outcome: Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant

Time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment. Number. Unit: percentage of participants

Measure	Adjusted MMF + Tacrolimus + CS n = 87	Fixed-Dose MMF + Tacrolimus + CS n = 87
Value	8.0	8.2

Population analysed: ITT population

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded from study start to 28 days after Month 12 or the last dose of study treatment.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Adjusted MMF + Tacrolimus + CS	70 of 91 (76.9%)	91 of 91 (100%)	Not reported
Fixed-Dose MMF + Tacrolimus + CS	69 of 92 (75%)	91 of 92 (98.9%)	Not reported

Limitations and caveats (from the sponsor): Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

16 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Mycophenolate mofetil, adjusted dose, Tacrolimus and Corticosteroids, IV in people with Liver Transplantation, run by Hoffmann-La Roche at 16 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant (time frame: Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00545402.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2014.