A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00545402
Collaborator
(none)
180
16
2
44
11.3
0.3
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
180 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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.
Study Start Date
:
Nov 1, 2007
Actual Primary Completion Date
:
Jul 1, 2011
Actual Study Completion Date
:
Jul 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MMF, Adjusted Dose; Tacrolimus; Corticosteroids 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. |
Drug: Mycophenolate mofetil, adjusted dose
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.
Other Names:
Drug: Tacrolimus
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
Drug: Corticosteroids, IV
10-15 mg/kg IV pre-operation on Day 0
Other Names:
|
| Active Comparator: MMF, Standard Dose; Tacrolimus; Corticosteroids 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. |
Drug: Tacrolimus
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
Drug: Corticosteroids, IV
10-15 mg/kg IV pre-operation on Day 0
Other Names:
Drug: Mycophenolate mofetil, Standard dose
2 g/d PO BID during meals from Day 0 to Month 12
Other Names:
Drug: Corticosteroids, PO
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant [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.
Secondary Outcome Measures
- Percentage of Participants With Graft Loss [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 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.
- Graft Survival [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.]
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.
- Overall Survival (OS) at Month 12 - Percentage of Participants With an Event [Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12]
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.
- Overall Survival at Month 12 [Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 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.
- Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review [Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12]
The percentage of participants with biopsies of grafts evaluated by central review and scored according to Banff criteria at Month 12 post-transplant.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adult patients, >=18 years of age;
-
recipient of a first orthotopic liver transplant.
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Besancon | France | 25030 | ||
| 2 | Bordeaux | France | 33076 | ||
| 3 | Caen | France | 14033 | ||
| 4 | Clichy | France | 92118 | ||
| 5 | Creteil | France | 94010 | ||
| 6 | Grenoble | France | 38043 | ||
| 7 | Lille | France | 59037 | ||
| 8 | Lyon cedex 3 | France | 69437 | ||
| 9 | Lyon | France | 69317 | ||
| 10 | Marseille | France | 13385 | ||
| 11 | Montpellier | France | 34295 | ||
| 12 | Nice | France | 06202 | ||
| 13 | Paris | France | 75679 | ||
| 14 | Rennes | France | 35033 | ||
| 15 | Toulouse | France | 31059 | ||
| 16 | Villejuif | France | 94804 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00545402
Other Study ID Numbers:
- ML21273
First Posted:
Oct 17, 2007
Last Update Posted:
Jul 14, 2014
Last Verified:
Jun 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Adjusted Mycophenolate Mofetil (MMF)+Tacrolimus+Corticosteroid | Fixed-Dose MMF + Tacrolimus + Corticosteroid (CS) |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 grams per day (g/d), orally (PO), twice daily (BID) with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (area under the concentration-time curve [AUC]) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 nanograms per milliliter (ng/mL) from Day 0 through 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 an intravenous (IV) bolus of methylprednisolone 10-15 milligrams per kilogram (mg/kg) pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Period Title: Overall Study | ||
| STARTED | 90 | 90 |
| COMPLETED | 56 | 61 |
| NOT COMPLETED | 34 | 29 |
Baseline Characteristics
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS | Total |
|---|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. | Total of all reporting groups |
| Overall Participants | 90 | 90 | 180 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
53.4
(8.5)
|
55.1
(8.3)
|
54.2
(8.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
16
17.8%
|
19
21.1%
|
35
19.4%
|
| Male |
74
82.2%
|
71
78.9%
|
145
80.6%
|
Outcome Measures
| Title | Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Measure Participants | 87 | 87 |
| Number [percentage of participants] |
8.0
8.9%
|
8.2
9.1%
|
| Title | Percentage of Participants With Graft Loss |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Measure Participants | 90 | 90 |
| Number [percentage of participants] |
2.2
2.4%
|
5.6
6.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Adjusted MMF + Tacrolimus + CS, Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2611 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Graft Survival |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Measure Participants | 90 | 90 |
| Median (Full Range) [months] |
12.9
|
12.9
|
| Title | Overall Survival (OS) at Month 12 - Percentage of Participants With an Event |
|---|---|
| Description | 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. |
| Time Frame | Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Measure Participants | 90 | 90 |
| Number [percentage of participants] |
8.9
9.9%
|
11.1
12.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Adjusted MMF + Tacrolimus + CS, Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7091 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Overall Survival at Month 12 |
|---|---|
| Description | 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. |
| Time Frame | Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Measure Participants | 90 | 90 |
| Median (Full Range) [months] |
12.9
|
12.9
|
| Title | Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review |
|---|---|
| Description | The percentage of participants with biopsies of grafts evaluated by central review and scored according to Banff criteria at Month 12 post-transplant. |
| Time Frame | Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; only participants with evaluable biopsies were included in the analysis. |
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. |
| Measure Participants | 42 | 35 |
| Normal liver |
4.8
5.3%
|
11.4
12.7%
|
| Minor lesions |
4.8
5.3%
|
17.1
19%
|
| Acute rejection |
0.0
0%
|
0.0
0%
|
| Chronic rejection |
7.1
7.9%
|
2.9
3.2%
|
| Chronic hepatitis |
26.2
29.1%
|
22.9
25.4%
|
| Vascular lesions |
35.7
39.7%
|
11.4
12.7%
|
| Pathology of biliary obstruction |
4.8
5.3%
|
5.7
6.3%
|
| Lobular hepatitis |
4.8
5.3%
|
2.9
3.2%
|
| Recurrence of initial autoimmune disease |
0.0
0%
|
0.0
0%
|
| Other |
35.7
39.7%
|
45.7
50.8%
|
Adverse Events
| Time Frame | Adverse events were recorded from study start to 28 days after Month 12 or the last dose of study treatment. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who were randomized and received at least one dose of MMF and/or corticosteroids were included in the safety analysis. Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events. | |||
| Arm/Group Title | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS | ||
| Arm/Group Description | Participants received MMF tablets or capsules, 3 g/d, PO, BID with meals from Day 0 to Day 4; thereafter the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14 and Months 1, 3, 6, 9, and 12. Participants also received tacrolimus capsules, adjusted to a target trough level of 8-12 ng/mL from Day 0 through 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 an IV bolus of methylprednisolone 10-15 mg/kg pre-operative on Day 0 per standard practice of the center. | Participants received MMF capsules or tablets, 2 g/d, PO, BID with meals from Day 0 to Month 12; tacrolimus capsules, 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; and IV bolus of prednisone, 10-15 mg/kg, pre-operative on Day 0 followed by prednisone tablets, 20 mg/d, PO, from Day 0 through Month 1; 15 mg/d, PO, from the end of Month 1 through Month 2; 10 mg/d, PO, from the end of Month 2 through Month 3; and 5 mg/d from the end of Month 3 through Month 6. Prednisone was discontinued from Month 7 through end of treatment. | ||
All Cause Mortality |
||||
| Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/91 (76.9%) | 69/92 (75%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/91 (0%) | 3/92 (3.3%) | ||
| Neutropenia | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Agranulocytosis | 2/91 (2.2%) | 0/92 (0%) | ||
| Febrile neutropenia | 2/91 (2.2%) | 0/92 (0%) | ||
| Leukopenia | 2/91 (2.2%) | 0/92 (0%) | ||
| Pancytopenia | 2/91 (2.2%) | 0/92 (0%) | ||
| Coagulopathy | 0/91 (0%) | 1/92 (1.1%) | ||
| Haemolytic anaemia | 1/91 (1.1%) | 0/92 (0%) | ||
| Cardiac disorders | ||||
| Ventricular tachycardia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Cardio-respiratory arrest | 1/91 (1.1%) | 0/92 (0%) | ||
| Cardiogenic shock | 1/91 (1.1%) | 0/92 (0%) | ||
| Myocardial infarction | 0/91 (0%) | 1/92 (1.1%) | ||
| Congenital, familial and genetic disorders | ||||
| Hereditary neuropathic amyloidosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Endocrine disorders | ||||
| Hyperparathyroidism | 0/91 (0%) | 1/92 (1.1%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 6/91 (6.6%) | 2/92 (2.2%) | ||
| Inguinal hernia | 2/91 (2.2%) | 4/92 (4.3%) | ||
| Ascites | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Abdominal hernia | 3/91 (3.3%) | 0/92 (0%) | ||
| Peritonitis | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Abdominal pain upper | 0/91 (0%) | 2/92 (2.2%) | ||
| Pancreatitis | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Peritoneal haemorrhage | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Umbilical hernia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Vomiting | 2/91 (2.2%) | 0/92 (0%) | ||
| Abdominal wall haematoma | 1/91 (1.1%) | 0/92 (0%) | ||
| Gastrointestinal disorder | 0/91 (0%) | 1/92 (1.1%) | ||
| Gastrointestinal necrosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Intestinal haemorrhage | 1/91 (1.1%) | 0/92 (0%) | ||
| Intra-abdominal haemorrhage | 1/91 (1.1%) | 0/92 (0%) | ||
| Pancreatitis acute | 0/91 (0%) | 1/92 (1.1%) | ||
| Small intestinal obstruction | 1/91 (1.1%) | 0/92 (0%) | ||
| Volvulus of small bowel | 0/91 (0%) | 1/92 (1.1%) | ||
| General disorders | ||||
| Multi-organ failure | 5/91 (5.5%) | 3/92 (3.3%) | ||
| General physical health deterioration | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Chest pain | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Pyrexia | 0/91 (0%) | 2/92 (2.2%) | ||
| Sudden death | 0/91 (0%) | 2/92 (2.2%) | ||
| Hyperthermia | 0/91 (0%) | 1/92 (1.1%) | ||
| Inflammation | 1/91 (1.1%) | 0/92 (0%) | ||
| Malaise | 1/91 (1.1%) | 0/92 (0%) | ||
| Ulcer haemorrhage | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stenosis | 2/91 (2.2%) | 4/92 (4.3%) | ||
| Cholangitis | 2/91 (2.2%) | 4/92 (4.3%) | ||
| Hepatic artery thrombosis | 1/91 (1.1%) | 5/92 (5.4%) | ||
| Hepatic artery stenosis | 3/91 (3.3%) | 2/92 (2.2%) | ||
| Biliary fistula | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Cholestasis | 0/91 (0%) | 4/92 (4.3%) | ||
| Cytolytic hepatitis | 0/91 (0%) | 2/92 (2.2%) | ||
| Bile duct necrosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Biliary cyst | 0/91 (0%) | 1/92 (1.1%) | ||
| Biliary tract disorder | 1/91 (1.1%) | 0/92 (0%) | ||
| Cholelithiasis | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatic artery aneurysm | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatic ischaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Hepatic vein stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Portal vein thrombosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Immune system disorders | ||||
| Liver transplant rejection | 0/91 (0%) | 1/92 (1.1%) | ||
| Infections and infestations | ||||
| Hepatitis C | 3/91 (3.3%) | 7/92 (7.6%) | ||
| Sepsis | 3/91 (3.3%) | 4/92 (4.3%) | ||
| Septic shock | 4/91 (4.4%) | 1/92 (1.1%) | ||
| Peritoneal infection | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Biliary sepsis | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Candida sepsis | 0/91 (0%) | 2/92 (2.2%) | ||
| Cytomegalovirus infection | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Appendicitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Arthritis bacterial | 1/91 (1.1%) | 0/92 (0%) | ||
| Aspergillosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Bacterial sepsis | 1/91 (1.1%) | 0/92 (0%) | ||
| Cytomegalovirus colitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Device related infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Enterocolitis infectious | 0/91 (0%) | 1/92 (1.1%) | ||
| Hepatitis E | 1/91 (1.1%) | 0/92 (0%) | ||
| Herpes zoster | 1/91 (1.1%) | 0/92 (0%) | ||
| Infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Liver abscess | 0/91 (0%) | 1/92 (1.1%) | ||
| Nocardiosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Pneumocystis jiroveci pneumonia | 0/91 (0%) | 1/92 (1.1%) | ||
| Pneumonia | 0/91 (0%) | 1/92 (1.1%) | ||
| Pneumonia cytomegaloviral | 1/91 (1.1%) | 0/92 (0%) | ||
| Systemic candida | 1/91 (1.1%) | 0/92 (0%) | ||
| Urinary tract infection | 0/91 (0%) | 1/92 (1.1%) | ||
| Viral diarrhoea | 1/91 (1.1%) | 0/92 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Biliary anastomosis complication | 5/91 (5.5%) | 6/92 (6.5%) | ||
| Anastomotic stenosis | 0/91 (0%) | 4/92 (4.3%) | ||
| Graft dysfunction | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Overdose | 0/91 (0%) | 2/92 (2.2%) | ||
| Wound dehiscence | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Complications of transplant surgery | 0/91 (0%) | 1/92 (1.1%) | ||
| Complications of transplanted liver | 1/91 (1.1%) | 0/92 (0%) | ||
| Endotracheal intubation complication | 1/91 (1.1%) | 0/92 (0%) | ||
| Femoral neck fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Graft thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Post procedural haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Wound evisceration | 0/91 (0%) | 1/92 (1.1%) | ||
| Wound secretion | 0/91 (0%) | 1/92 (1.1%) | ||
| Investigations | ||||
| Liver function test abnormal | 0/91 (0%) | 3/92 (3.3%) | ||
| Cytomegalovirus antibody positive | 0/91 (0%) | 1/92 (1.1%) | ||
| Oesophagogastroduodenoscopy | 1/91 (1.1%) | 0/92 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 0/91 (0%) | 3/92 (3.3%) | ||
| Hyperkalaemia | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Type 1 diabetes mellitus | 0/91 (0%) | 2/92 (2.2%) | ||
| Cell death | 1/91 (1.1%) | 0/92 (0%) | ||
| Diabetes mellitus inadequate control | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Osteoarthritis | 0/91 (0%) | 2/92 (2.2%) | ||
| Musculoskeletal pain | 1/91 (1.1%) | 0/92 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Hepatic neoplasm malignant | 0/91 (0%) | 1/92 (1.1%) | ||
| Lung neoplasm malignant | 0/91 (0%) | 1/92 (1.1%) | ||
| Metastases to bone | 0/91 (0%) | 1/92 (1.1%) | ||
| Metastases to spine | 1/91 (1.1%) | 0/92 (0%) | ||
| Prostate cancer | 0/91 (0%) | 1/92 (1.1%) | ||
| Thyroid neoplasm | 1/91 (1.1%) | 0/92 (0%) | ||
| Nervous system disorders | ||||
| Encephalopathy | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Epilepsy | 2/91 (2.2%) | 0/92 (0%) | ||
| Cerebral haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Cerebral ischaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Cerebrovascular accident | 1/91 (1.1%) | 0/92 (0%) | ||
| Coma | 0/91 (0%) | 1/92 (1.1%) | ||
| Convulsion | 1/91 (1.1%) | 0/92 (0%) | ||
| Febrile convulsion | 1/91 (1.1%) | 0/92 (0%) | ||
| Metabolic encephalopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Neuropathy peripheral | 0/91 (0%) | 1/92 (1.1%) | ||
| Toxic encephalopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Vocal cord paresis | 0/91 (0%) | 1/92 (1.1%) | ||
| Psychiatric disorders | ||||
| Confusional state | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Mental disorder | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Delirium | 0/91 (0%) | 1/92 (1.1%) | ||
| Depression | 0/91 (0%) | 1/92 (1.1%) | ||
| Renal and urinary disorders | ||||
| Renal failure acute | 14/91 (15.4%) | 5/92 (5.4%) | ||
| Renal failure | 6/91 (6.6%) | 6/92 (6.5%) | ||
| Ureteric stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Reproductive system and breast disorders | ||||
| Prostatitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Testicular torsion | 0/91 (0%) | 1/92 (1.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Lung disorder | 5/91 (5.5%) | 4/92 (4.3%) | ||
| Pleural effusion | 1/91 (1.1%) | 3/92 (3.3%) | ||
| Acute respiratory distress syndrome | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Pulmonary embolism | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Bronchopneumopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Hypoxia | 1/91 (1.1%) | 0/92 (0%) | ||
| Pulmonary oedema | 1/91 (1.1%) | 0/92 (0%) | ||
| Respiratory failure | 0/91 (0%) | 1/92 (1.1%) | ||
| Surgical and medical procedures | ||||
| Biliary anastomosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Biliary drainage | 1/91 (1.1%) | 0/92 (0%) | ||
| Catheter removal | 0/91 (0%) | 1/92 (1.1%) | ||
| Surgical vascular shunt | 0/91 (0%) | 1/92 (1.1%) | ||
| Vascular disorders | ||||
| Shock haemorrhagic | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Arterial haemorrhage | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Aneurysm | 1/91 (1.1%) | 0/92 (0%) | ||
| Angiopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Arterial stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Arterial thrombosis limb | 0/91 (0%) | 1/92 (1.1%) | ||
| Haematoma | 0/91 (0%) | 1/92 (1.1%) | ||
| Haemodynamic instability | 0/91 (0%) | 1/92 (1.1%) | ||
| Jugular vein thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Vascular stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Venous thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 91/91 (100%) | 91/92 (98.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 45/91 (49.5%) | 44/92 (47.8%) | ||
| Thrombocytopenia | 16/91 (17.6%) | 13/92 (14.1%) | ||
| Neutropenia | 13/91 (14.3%) | 6/92 (6.5%) | ||
| Leukopenia | 14/91 (15.4%) | 2/92 (2.2%) | ||
| Pancytopenia | 11/91 (12.1%) | 4/92 (4.3%) | ||
| Deficiency anaemia | 6/91 (6.6%) | 3/92 (3.3%) | ||
| Leukocytosis | 1/91 (1.1%) | 3/92 (3.3%) | ||
| Lymphopenia | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Agranulocytosis | 2/91 (2.2%) | 0/92 (0%) | ||
| Disseminated intravascular coagulation | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Febrile neutropenia | 2/91 (2.2%) | 0/92 (0%) | ||
| Bone marrow failure | 0/91 (0%) | 1/92 (1.1%) | ||
| Coagulopathy | 0/91 (0%) | 1/92 (1.1%) | ||
| Febrile bone marrow aplasia | 1/91 (1.1%) | 0/92 (0%) | ||
| Haemolytic anaemia | 1/91 (1.1%) | 0/92 (0%) | ||
| Idiopathic thrombocytopenic purpura | 0/91 (0%) | 1/92 (1.1%) | ||
| Iron deficiency anaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Jaundice acholuric | 1/91 (1.1%) | 0/92 (0%) | ||
| Lymphadenopathy | 0/91 (0%) | 1/92 (1.1%) | ||
| Polycythaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Splenomegaly | 0/91 (0%) | 1/92 (1.1%) | ||
| Thrombocythaemia | 1/91 (1.1%) | 0/92 (0%) | ||
| Thrombotic microangiopathy | 0/91 (0%) | 1/92 (1.1%) | ||
| Cardiac disorders | ||||
| Tachycardia | 6/91 (6.6%) | 1/92 (1.1%) | ||
| Atrial fibrillation | 3/91 (3.3%) | 3/92 (3.3%) | ||
| Acute coronary syndrome | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Arrhythmia | 0/91 (0%) | 3/92 (3.3%) | ||
| Bradycardia | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Pericardial effusion | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Supraventricular tachycardia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Ventricular tachycardia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Arrhythmia supraventricular | 0/91 (0%) | 1/92 (1.1%) | ||
| Atrial flutter | 1/91 (1.1%) | 0/92 (0%) | ||
| Cardiac failure | 1/91 (1.1%) | 0/92 (0%) | ||
| Cardio-respiratory arrest | 1/91 (1.1%) | 0/92 (0%) | ||
| Cardiogenic shock | 1/91 (1.1%) | 0/92 (0%) | ||
| Cardiomyopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Myocardial infarction | 0/91 (0%) | 1/92 (1.1%) | ||
| Palpitations | 1/91 (1.1%) | 0/92 (0%) | ||
| Pericardial disease | 1/91 (1.1%) | 0/92 (0%) | ||
| Stress cardiomyopathy | 0/91 (0%) | 1/92 (1.1%) | ||
| Ventricular extrasystoles | 0/91 (0%) | 1/92 (1.1%) | ||
| Congenital, familial and genetic disorders | ||||
| Hereditary neuropathic amyloidosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Hydrocele | 1/91 (1.1%) | 0/92 (0%) | ||
| Ear and labyrinth disorders | ||||
| Ear haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Ear pain | 0/91 (0%) | 1/92 (1.1%) | ||
| Endocrine disorders | ||||
| Hyperparathyroidism | 0/91 (0%) | 1/92 (1.1%) | ||
| Hyperthyroidism | 1/91 (1.1%) | 0/92 (0%) | ||
| Eye disorders | ||||
| Visual acuity reduced | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Visual disturbance | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Uveitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 31/91 (34.1%) | 26/92 (28.3%) | ||
| Abdominal pain | 12/91 (13.2%) | 12/92 (13%) | ||
| Ascites | 9/91 (9.9%) | 11/92 (12%) | ||
| Constipation | 8/91 (8.8%) | 11/92 (12%) | ||
| Nausea | 8/91 (8.8%) | 8/92 (8.7%) | ||
| Vomiting | 10/91 (11%) | 5/92 (5.4%) | ||
| Gastrointestinal disorder | 2/91 (2.2%) | 7/92 (7.6%) | ||
| Inguinal hernia | 2/91 (2.2%) | 7/92 (7.6%) | ||
| Abdominal pain upper | 2/91 (2.2%) | 5/92 (5.4%) | ||
| Dyspepsia | 2/91 (2.2%) | 3/92 (3.3%) | ||
| Peritonitis | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Abdominal hernia | 3/91 (3.3%) | 0/92 (0%) | ||
| Dysphagia | 0/91 (0%) | 2/92 (2.2%) | ||
| Gastrooesophageal reflux disease | 0/91 (0%) | 2/92 (2.2%) | ||
| Impaired gastric emptying | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Intra-abdominal haemorrhage | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Pancreatitis | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Pancreatitis acute | 0/91 (0%) | 2/92 (2.2%) | ||
| Peritoneal haemorrhage | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Subileus | 2/91 (2.2%) | 0/92 (0%) | ||
| Umbilical hernia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Abdominal wall haematoma | 1/91 (1.1%) | 0/92 (0%) | ||
| Coeliac artery stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Colitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Duodenal ulcer | 1/91 (1.1%) | 0/92 (0%) | ||
| Duodenal ulcer haemorrhage | 1/91 (1.1%) | 0/92 (0%) | ||
| Duodenitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Gastric ulcer | 1/91 (1.1%) | 0/92 (0%) | ||
| Gastritis | 1/91 (1.1%) | 0/92 (0%) | ||
| Gastritis erosive | 0/91 (0%) | 1/92 (1.1%) | ||
| Gastrointestinal motility disorder | 0/91 (0%) | 1/92 (1.1%) | ||
| Gastrointestinal necrosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Gastrointestinal pain | 1/91 (1.1%) | 0/92 (0%) | ||
| Haematemesis | 0/91 (0%) | 1/92 (1.1%) | ||
| Haemorrhoids | 0/91 (0%) | 1/92 (1.1%) | ||
| Intestinal haemorrhage | 1/91 (1.1%) | 0/92 (0%) | ||
| Intestinal obstruction | 1/91 (1.1%) | 0/92 (0%) | ||
| Melaena | 0/91 (0%) | 1/92 (1.1%) | ||
| Oesophageal ulcer | 1/91 (1.1%) | 0/92 (0%) | ||
| Oesophagitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Oesophagitis ulcerative | 0/91 (0%) | 1/92 (1.1%) | ||
| Peritoneal effusion | 0/91 (0%) | 1/92 (1.1%) | ||
| Pneumoperitoneum | 1/91 (1.1%) | 0/92 (0%) | ||
| Portal venous gas | 1/91 (1.1%) | 0/92 (0%) | ||
| Small bowel angioedema | 0/91 (0%) | 1/92 (1.1%) | ||
| Small intestinal obstruction | 1/91 (1.1%) | 0/92 (0%) | ||
| Stomatitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Toothache | 1/91 (1.1%) | 0/92 (0%) | ||
| Volvulus of small bowel | 0/91 (0%) | 1/92 (1.1%) | ||
| General disorders | ||||
| Oedema peripheral | 10/91 (11%) | 17/92 (18.5%) | ||
| Pain | 12/91 (13.2%) | 10/92 (10.9%) | ||
| Pyrexia | 11/91 (12.1%) | 4/92 (4.3%) | ||
| Hyperthermia | 8/91 (8.8%) | 5/92 (5.4%) | ||
| Oedema | 7/91 (7.7%) | 5/92 (5.4%) | ||
| Multi-organ failure | 5/91 (5.5%) | 5/92 (5.4%) | ||
| Asthenia | 2/91 (2.2%) | 6/92 (6.5%) | ||
| Inflammation | 2/91 (2.2%) | 5/92 (5.4%) | ||
| Chest pain | 2/91 (2.2%) | 2/92 (2.2%) | ||
| General physical health deterioration | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Hypothermia | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Effusion | 2/91 (2.2%) | 0/92 (0%) | ||
| Influenza like illness | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Sudden death | 0/91 (0%) | 2/92 (2.2%) | ||
| Catheter site necrosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Chills | 0/91 (0%) | 1/92 (1.1%) | ||
| Generalised oedema | 1/91 (1.1%) | 0/92 (0%) | ||
| Malaise | 1/91 (1.1%) | 0/92 (0%) | ||
| Necrosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Polyp | 1/91 (1.1%) | 0/92 (0%) | ||
| Ulcer | 1/91 (1.1%) | 0/92 (0%) | ||
| Ulcer haemorrhage | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholestasis | 24/91 (26.4%) | 19/92 (20.7%) | ||
| Cholangitis | 5/91 (5.5%) | 6/92 (6.5%) | ||
| Bile duct stenosis | 4/91 (4.4%) | 4/92 (4.3%) | ||
| Hepatic artery thrombosis | 1/91 (1.1%) | 7/92 (7.6%) | ||
| Cytolytic hepatitis | 4/91 (4.4%) | 3/92 (3.3%) | ||
| Hepatic artery stenosis | 4/91 (4.4%) | 3/92 (3.3%) | ||
| Jaundice | 5/91 (5.5%) | 2/92 (2.2%) | ||
| Biliary fistula | 3/91 (3.3%) | 3/92 (3.3%) | ||
| Portal vein thrombosis | 5/91 (5.5%) | 1/92 (1.1%) | ||
| Biloma | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Biliary tract disorder | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Hepatic function abnormal | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Biliary cyst | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Hepatic cirrhosis | 2/91 (2.2%) | 0/92 (0%) | ||
| Hepatic failure | 0/91 (0%) | 2/92 (2.2%) | ||
| Hyperbilirubinaemia | 2/91 (2.2%) | 0/92 (0%) | ||
| Bile duct necrosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Cholelithiasis | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatic artery aneurysm | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatic ischaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Hepatic vein stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Hepatitis cholestatic | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatorenal syndrome | 1/91 (1.1%) | 0/92 (0%) | ||
| Immune system disorders | ||||
| Drug hypersensitivity | 1/91 (1.1%) | 3/92 (3.3%) | ||
| Hypersensitivity | 0/91 (0%) | 1/92 (1.1%) | ||
| Liver transplant rejection | 0/91 (0%) | 1/92 (1.1%) | ||
| Transplant rejection | 0/91 (0%) | 1/92 (1.1%) | ||
| Infections and infestations | ||||
| Urinary tract infection | 13/91 (14.3%) | 14/92 (15.2%) | ||
| Hepatitis C | 7/91 (7.7%) | 11/92 (12%) | ||
| Sepsis | 9/91 (9.9%) | 8/92 (8.7%) | ||
| Cytomegalovirus infection | 7/91 (7.7%) | 6/92 (6.5%) | ||
| Staphylococcal infection | 4/91 (4.4%) | 6/92 (6.5%) | ||
| Bronchitis | 2/91 (2.2%) | 5/92 (5.4%) | ||
| Septic shock | 4/91 (4.4%) | 2/92 (2.2%) | ||
| Infection | 4/91 (4.4%) | 1/92 (1.1%) | ||
| Puncture site infection | 3/91 (3.3%) | 2/92 (2.2%) | ||
| Abdominal wall abscess | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Ascites infection | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Enterococcal infection | 4/91 (4.4%) | 0/92 (0%) | ||
| Lung infection | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Peritoneal infection | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Nasopharyngitis | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Oral candidiasis | 0/91 (0%) | 3/92 (3.3%) | ||
| Staphylococcal sepsis | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Tonsillitis | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Arthritis bacterial | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Biliary sepsis | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Candida sepsis | 0/91 (0%) | 2/92 (2.2%) | ||
| Catheter related infection | 0/91 (0%) | 2/92 (2.2%) | ||
| Clostridial infection | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Device related infection | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Fungal infection | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Gastroenteritis viral | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Herpes zoster | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Postoperative wound infection | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Streptococcal infection | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Abscess | 1/91 (1.1%) | 0/92 (0%) | ||
| Appendicitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Aspergillosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Bacterial infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Bacterial sepsis | 1/91 (1.1%) | 0/92 (0%) | ||
| Bronchopulmonary aspergillosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Candidiasis | 1/91 (1.1%) | 0/92 (0%) | ||
| Cellulitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Cholecystitis infective | 0/91 (0%) | 1/92 (1.1%) | ||
| Citrobacter infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Clostridium difficile colitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Cystitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Cytomegalovirus colitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Cytomegalovirus viraemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Endocarditis | 0/91 (0%) | 1/92 (1.1%) | ||
| Enterobacter bacteraemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Enterocolitis infectious | 0/91 (0%) | 1/92 (1.1%) | ||
| Furuncle | 0/91 (0%) | 1/92 (1.1%) | ||
| Hepatitis E | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatobiliary infection | 0/91 (0%) | 1/92 (1.1%) | ||
| Herpes simplex | 0/91 (0%) | 1/92 (1.1%) | ||
| Influenza | 1/91 (1.1%) | 0/92 (0%) | ||
| Infusion site infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Liver abscess | 0/91 (0%) | 1/92 (1.1%) | ||
| Nocardiosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Oesophageal candidiasis | 1/91 (1.1%) | 0/92 (0%) | ||
| Oral fungal infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Orchitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Paronychia | 1/91 (1.1%) | 0/92 (0%) | ||
| Pneumocystis jiroveci pneumonia | 0/91 (0%) | 1/92 (1.1%) | ||
| Pneumonia | 0/91 (0%) | 1/92 (1.1%) | ||
| Pneumonia cytomegaloviral | 1/91 (1.1%) | 0/92 (0%) | ||
| Pseudomonal sepsis | 1/91 (1.1%) | 0/92 (0%) | ||
| Rhinitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Serratia infection | 0/91 (0%) | 1/92 (1.1%) | ||
| Skin infection | 1/91 (1.1%) | 0/92 (0%) | ||
| Staphylococcal bacteraemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Systemic candida | 1/91 (1.1%) | 0/92 (0%) | ||
| Viral diarrhoea | 1/91 (1.1%) | 0/92 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Biliary anastomosis complication | 7/91 (7.7%) | 6/92 (6.5%) | ||
| Seroma | 4/91 (4.4%) | 5/92 (5.4%) | ||
| Overdose | 1/91 (1.1%) | 6/92 (6.5%) | ||
| Anastomotic stenosis | 2/91 (2.2%) | 4/92 (4.3%) | ||
| Eschar | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Hepatic haematoma | 1/91 (1.1%) | 3/92 (3.3%) | ||
| Procedural pain | 4/91 (4.4%) | 0/92 (0%) | ||
| Wound dehiscence | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Accidental overdose | 3/91 (3.3%) | 0/92 (0%) | ||
| Graft dysfunction | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Operative haemorrhage | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Endotracheal intubation complication | 2/91 (2.2%) | 0/92 (0%) | ||
| Complications of transplant surgery | 0/91 (0%) | 1/92 (1.1%) | ||
| Complications of transplanted liver | 1/91 (1.1%) | 0/92 (0%) | ||
| Facial bones fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Fall | 0/91 (0%) | 1/92 (1.1%) | ||
| Femoral neck fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Foot fracture | 1/91 (1.1%) | 0/92 (0%) | ||
| Graft thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Poisoning | 0/91 (0%) | 1/92 (1.1%) | ||
| Post procedural haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Radiation leukopenia | 1/91 (1.1%) | 0/92 (0%) | ||
| Radiation oesophagitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Rib fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Spinal compression fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Surgical procedure repeated | 1/91 (1.1%) | 0/92 (0%) | ||
| Thoracic vertebral fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Tooth fracture | 0/91 (0%) | 1/92 (1.1%) | ||
| Wound | 1/91 (1.1%) | 0/92 (0%) | ||
| Wound evisceration | 0/91 (0%) | 1/92 (1.1%) | ||
| Wound secretion | 0/91 (0%) | 1/92 (1.1%) | ||
| Investigations | ||||
| Band neutrophil percentage decreased | 4/91 (4.4%) | 5/92 (5.4%) | ||
| Weight decreased | 4/91 (4.4%) | 5/92 (5.4%) | ||
| Red blood cell count decreased | 3/91 (3.3%) | 4/92 (4.3%) | ||
| Liver function test abnormal | 1/91 (1.1%) | 5/92 (5.4%) | ||
| Weight increased | 3/91 (3.3%) | 2/92 (2.2%) | ||
| Gamma-glutamyltransferase increased | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Blood bilirubin increased | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Blood urea increased | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Haematology test abnormal | 0/91 (0%) | 2/92 (2.2%) | ||
| Aspiration tracheal | 1/91 (1.1%) | 0/92 (0%) | ||
| Blood glucose | 1/91 (1.1%) | 0/92 (0%) | ||
| Cytomegalovirus antibody positive | 0/91 (0%) | 1/92 (1.1%) | ||
| Oesophagogastroduodenoscopy | 1/91 (1.1%) | 0/92 (0%) | ||
| Prothrombin level decreased | 1/91 (1.1%) | 0/92 (0%) | ||
| Serum ferritin increased | 0/91 (0%) | 1/92 (1.1%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperkalaemia | 15/91 (16.5%) | 14/92 (15.2%) | ||
| Diabetes mellitus | 6/91 (6.6%) | 19/92 (20.7%) | ||
| Hyperglycaemia | 11/91 (12.1%) | 13/92 (14.1%) | ||
| Cell death | 12/91 (13.2%) | 8/92 (8.7%) | ||
| Hypokalaemia | 5/91 (5.5%) | 8/92 (8.7%) | ||
| Diabetes mellitus inadequate control | 5/91 (5.5%) | 3/92 (3.3%) | ||
| Dyslipidaemia | 1/91 (1.1%) | 5/92 (5.4%) | ||
| Type 1 diabetes mellitus | 1/91 (1.1%) | 4/92 (4.3%) | ||
| Anorexia | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Hypomagnesaemia | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Hypercalcaemia | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Hypercholesterolaemia | 0/91 (0%) | 3/92 (3.3%) | ||
| Hypoalbuminaemia | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Acidosis | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Electrolyte imbalance | 0/91 (0%) | 2/92 (2.2%) | ||
| Hypocalcaemia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Hypoglycaemia | 0/91 (0%) | 2/92 (2.2%) | ||
| Iron deficiency | 0/91 (0%) | 2/92 (2.2%) | ||
| Metabolic acidosis | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Weight fluctuation | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Cachexia | 1/91 (1.1%) | 0/92 (0%) | ||
| Decreased appetite | 0/91 (0%) | 1/92 (1.1%) | ||
| Dehydration | 1/91 (1.1%) | 0/92 (0%) | ||
| Fluid overload | 0/91 (0%) | 1/92 (1.1%) | ||
| Gout | 1/91 (1.1%) | 0/92 (0%) | ||
| Hypernatraemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Hypertriglyceridaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Hyponatraemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Hypovitaminosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Lactic acidosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Metabolic syndrome | 1/91 (1.1%) | 0/92 (0%) | ||
| Mineral deficiency | 0/91 (0%) | 1/92 (1.1%) | ||
| Phlebitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 7/91 (7.7%) | 7/92 (7.6%) | ||
| Muscle spasms | 5/91 (5.5%) | 4/92 (4.3%) | ||
| Osteopenia | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Osteoporosis | 1/91 (1.1%) | 3/92 (3.3%) | ||
| Pain in extremity | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Osteoarthritis | 0/91 (0%) | 3/92 (3.3%) | ||
| Arthralgia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Hypercreatinaemia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Musculoskeletal pain | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Amyotrophy | 1/91 (1.1%) | 0/92 (0%) | ||
| Bursitis | 1/91 (1.1%) | 0/92 (0%) | ||
| Intervertebral disc protrusion | 0/91 (0%) | 1/92 (1.1%) | ||
| Muscle haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Musculoskeletal chest pain | 0/91 (0%) | 1/92 (1.1%) | ||
| Myalgia | 0/91 (0%) | 1/92 (1.1%) | ||
| Neck pain | 0/91 (0%) | 1/92 (1.1%) | ||
| Spinal osteoarthritis | 0/91 (0%) | 1/92 (1.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/91 (1.1%) | 0/92 (0%) | ||
| Hepatic neoplasm malignant | 0/91 (0%) | 1/92 (1.1%) | ||
| Lung neoplasm malignant | 0/91 (0%) | 1/92 (1.1%) | ||
| Metastases to bone | 0/91 (0%) | 1/92 (1.1%) | ||
| Metastases to spine | 1/91 (1.1%) | 0/92 (0%) | ||
| Prostate cancer | 0/91 (0%) | 1/92 (1.1%) | ||
| Thyroid neoplasm | 1/91 (1.1%) | 0/92 (0%) | ||
| Nervous system disorders | ||||
| Headache | 9/91 (9.9%) | 10/92 (10.9%) | ||
| Tremor | 8/91 (8.8%) | 9/92 (9.8%) | ||
| Convulsion | 1/91 (1.1%) | 4/92 (4.3%) | ||
| Febrile convulsion | 4/91 (4.4%) | 1/92 (1.1%) | ||
| Encephalopathy | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Dizziness | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Dysarthria | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Epilepsy | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Paraesthesia | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Syncope vasovagal | 3/91 (3.3%) | 0/92 (0%) | ||
| Amnesia | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Carpal tunnel syndrome | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Ischaemic stroke | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Polyneuropathy | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Somnolence | 0/91 (0%) | 2/92 (2.2%) | ||
| Altered state of consciousness | 1/91 (1.1%) | 0/92 (0%) | ||
| Aphonia | 0/91 (0%) | 1/92 (1.1%) | ||
| Cerebral haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Cerebral ischaemia | 0/91 (0%) | 1/92 (1.1%) | ||
| Cerebrovascular accident | 1/91 (1.1%) | 0/92 (0%) | ||
| Cognitive disorder | 1/91 (1.1%) | 0/92 (0%) | ||
| Coma | 0/91 (0%) | 1/92 (1.1%) | ||
| Depressed level of consciousness | 0/91 (0%) | 1/92 (1.1%) | ||
| Hyperreflexia | 0/91 (0%) | 1/92 (1.1%) | ||
| Memory impairment | 0/91 (0%) | 1/92 (1.1%) | ||
| Metabolic encephalopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Neuropathy peripheral | 0/91 (0%) | 1/92 (1.1%) | ||
| Paresis | 0/91 (0%) | 1/92 (1.1%) | ||
| Psychomotor skills impaired | 1/91 (1.1%) | 0/92 (0%) | ||
| Subarachnoid haemorrhage | 0/91 (0%) | 1/92 (1.1%) | ||
| Toxic encephalopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Vocal cord paralysis | 1/91 (1.1%) | 0/92 (0%) | ||
| Vocal cord paresis | 0/91 (0%) | 1/92 (1.1%) | ||
| Psychiatric disorders | ||||
| Confusional state | 11/91 (12.1%) | 14/92 (15.2%) | ||
| Insomnia | 15/91 (16.5%) | 10/92 (10.9%) | ||
| Agitation | 8/91 (8.8%) | 8/92 (8.7%) | ||
| Anxiety | 4/91 (4.4%) | 12/92 (13%) | ||
| Depression | 1/91 (1.1%) | 6/92 (6.5%) | ||
| Delirium | 0/91 (0%) | 2/92 (2.2%) | ||
| Mental disorder | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Affective disorder | 0/91 (0%) | 1/92 (1.1%) | ||
| Hallucination | 0/91 (0%) | 1/92 (1.1%) | ||
| Hallucination, visual | 1/91 (1.1%) | 0/92 (0%) | ||
| Sleep disorder | 0/91 (0%) | 1/92 (1.1%) | ||
| Renal and urinary disorders | ||||
| Renal failure | 24/91 (26.4%) | 23/92 (25%) | ||
| Renal failure acute | 22/91 (24.2%) | 16/92 (17.4%) | ||
| Renal impairment | 6/91 (6.6%) | 8/92 (8.7%) | ||
| Oliguria | 4/91 (4.4%) | 5/92 (5.4%) | ||
| Anuria | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Dysuria | 0/91 (0%) | 2/92 (2.2%) | ||
| Micturition disorder | 0/91 (0%) | 1/92 (1.1%) | ||
| Polyuria | 0/91 (0%) | 1/92 (1.1%) | ||
| Renal colic | 0/91 (0%) | 1/92 (1.1%) | ||
| Renal pain | 0/91 (0%) | 1/92 (1.1%) | ||
| Renal tubular disorder | 1/91 (1.1%) | 0/92 (0%) | ||
| Ureteric stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Urinary incontinence | 0/91 (0%) | 1/92 (1.1%) | ||
| Urinary retention | 0/91 (0%) | 1/92 (1.1%) | ||
| Reproductive system and breast disorders | ||||
| Prostatitis | 0/91 (0%) | 2/92 (2.2%) | ||
| Benign prostatic hyperplasia | 0/91 (0%) | 1/92 (1.1%) | ||
| Oedema genital | 1/91 (1.1%) | 0/92 (0%) | ||
| Ovarian cyst | 1/91 (1.1%) | 0/92 (0%) | ||
| Pruritus genital | 0/91 (0%) | 1/92 (1.1%) | ||
| Testicular torsion | 0/91 (0%) | 1/92 (1.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pleural effusion | 22/91 (24.2%) | 25/92 (27.2%) | ||
| Lung disorder | 13/91 (14.3%) | 9/92 (9.8%) | ||
| Cough | 5/91 (5.5%) | 1/92 (1.1%) | ||
| Dyspnoea | 3/91 (3.3%) | 3/92 (3.3%) | ||
| Acute respiratory distress syndrome | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Atelectasis | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Hypoxia | 3/91 (3.3%) | 1/92 (1.1%) | ||
| Acute pulmonary oedema | 3/91 (3.3%) | 0/92 (0%) | ||
| Pulmonary embolism | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Respiratory distress | 1/91 (1.1%) | 2/92 (2.2%) | ||
| Bronchial obstruction | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Bronchopneumopathy | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Respiratory failure | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Dyspnoea exertional | 0/91 (0%) | 1/92 (1.1%) | ||
| Epistaxis | 0/91 (0%) | 1/92 (1.1%) | ||
| Hydropneumothorax | 0/91 (0%) | 1/92 (1.1%) | ||
| Hydrothorax | 1/91 (1.1%) | 0/92 (0%) | ||
| Pneumothorax | 1/91 (1.1%) | 0/92 (0%) | ||
| Pulmonary oedema | 1/91 (1.1%) | 0/92 (0%) | ||
| Respiratory gas exchange disorder | 1/91 (1.1%) | 0/92 (0%) | ||
| Rhinorrhoea | 1/91 (1.1%) | 0/92 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 8/91 (8.8%) | 3/92 (3.3%) | ||
| Skin necrosis | 1/91 (1.1%) | 4/92 (4.3%) | ||
| Erythema | 2/91 (2.2%) | 1/92 (1.1%) | ||
| Dermatitis exfoliative | 0/91 (0%) | 1/92 (1.1%) | ||
| Rash | 0/91 (0%) | 1/92 (1.1%) | ||
| Scar pain | 0/91 (0%) | 1/92 (1.1%) | ||
| Skin lesion | 0/91 (0%) | 1/92 (1.1%) | ||
| Urticaria | 0/91 (0%) | 1/92 (1.1%) | ||
| Vascular purpura | 1/91 (1.1%) | 0/92 (0%) | ||
| Social circumstances | ||||
| Alcohol use | 0/91 (0%) | 1/92 (1.1%) | ||
| Surgical and medical procedures | ||||
| Biliary anastomosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Biliary drainage | 1/91 (1.1%) | 0/92 (0%) | ||
| Catheter removal | 0/91 (0%) | 1/92 (1.1%) | ||
| Skin neoplasm excision | 1/91 (1.1%) | 0/92 (0%) | ||
| Surgical vascular shunt | 0/91 (0%) | 1/92 (1.1%) | ||
| Vascular disorders | ||||
| Hypertension | 31/91 (34.1%) | 31/92 (33.7%) | ||
| Venous thrombosis | 7/91 (7.7%) | 4/92 (4.3%) | ||
| Haemodynamic instability | 3/91 (3.3%) | 7/92 (7.6%) | ||
| Haemorrhage | 3/91 (3.3%) | 4/92 (4.3%) | ||
| Hypotension | 3/91 (3.3%) | 3/92 (3.3%) | ||
| Haematoma | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Shock haemorrhagic | 2/91 (2.2%) | 2/92 (2.2%) | ||
| Arterial haemorrhage | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Vein discolouration | 1/91 (1.1%) | 1/92 (1.1%) | ||
| Aneurysm | 1/91 (1.1%) | 0/92 (0%) | ||
| Angiopathy | 1/91 (1.1%) | 0/92 (0%) | ||
| Arterial stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Arterial thrombosis limb | 0/91 (0%) | 1/92 (1.1%) | ||
| Hypovolaemic shock | 0/91 (0%) | 1/92 (1.1%) | ||
| Jugular vein thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Lymphoedema | 1/91 (1.1%) | 0/92 (0%) | ||
| Orthostatic hypotension | 0/91 (0%) | 1/92 (1.1%) | ||
| Thrombophlebitis | 0/91 (0%) | 1/92 (1.1%) | ||
| Thrombosis | 1/91 (1.1%) | 0/92 (0%) | ||
| Vascular stenosis | 0/91 (0%) | 1/92 (1.1%) | ||
| Venous stasis | 1/91 (1.1%) | 0/92 (0%) | ||
Limitations/Caveats
Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffman-LaRoche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00545402
Other Study ID Numbers:
- ML21273
First Posted:
Oct 17, 2007
Last Update Posted:
Jul 14, 2014
Last Verified:
Jun 1, 2014