Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 20 of 66 for:    "Viral Infectious Disease" | "Mycophenolic acid"

Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection (REVERT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00582738
Recruitment Status : Terminated
First Posted : December 28, 2007
Results First Posted : September 6, 2012
Last Update Posted : September 6, 2012
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Recurrent Hepatitis C
Interventions Drug: CsA-TAC (standard Treatment)
Drug: Everolimus
Enrollment 43
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Standard Treatment Everolimus
Hide Arm/Group Description Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction. Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Period Title: Overall Study
Started 21 22
Completed 12 4
Not Completed 9 18
Reason Not Completed
Administrative Problems             7             8
Adverse Event             0             5
Graft Lost             0             1
Other             1             0
Protocol Violation             1             1
Withdrawal by Subject             0             3
Arm/Group Title Standard Treatment Everolimus Total
Hide Arm/Group Description Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction. Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids. Total of all reporting groups
Overall Number of Baseline Participants 21 22 43
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 21 participants 22 participants 43 participants
60.0
(43 to 70)
56.5
(41 to 69)
57
(41 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 22 participants 43 participants
Female
10
  47.6%
7
  31.8%
17
  39.5%
Male
11
  52.4%
15
  68.2%
26
  60.5%
1.Primary Outcome
Title Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.
Hide Description

Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite

Decrease in score from baseline indicates improvement

Time Frame baseline, 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. Small number of biopsies obtained at Month 24 due to study being prematurely terminated.
Arm/Group Title CsA-TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 8 5
Median (Full Range)
Unit of Measure: Score on Scale
-0.5
(-1.0 to 2.0)
0.0
(-1.0 to 0.0)
2.Secondary Outcome
Title Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization
Hide Description Metavir Score: F0=No fibrosis; F1=Portal fibrosis without septa; F2=Portal fibrosis with rare septa; F3=Numerous septa without cirrhosis Decrease in score from baseline indicates improvement
Time Frame Baseline, 12 months, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. Only participants with observations at baseline and specified timepoints were included in the analysis.
Arm/Group Title CsA-TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 18 14
Median (Full Range)
Unit of Measure: Scores on a Scale
Baseline (n=18, 14)
1.0
(1.0 to 4.0)
1.5
(1.0 to 3.0)
Month 12 (n=18, 14)
1.0
(0.0 to 4.0)
1.0
(0.0 to 3.0)
Month 24 (n=8, 5)
1.0
(0.0 to 3.0)
1.0
(1.0 to 3.0)
Month 12-Baseline (n=18, 14)
0.0
(-1.0 to 2.0)
0.0
(-2.0 to 1.0)
Month 24-Baseline (n=8, 5)
0.0
(-1.0 to 2.0)
0.0
(-1.0 to 0.0)
3.Secondary Outcome
Title Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups
Hide Description [Not Specified]
Time Frame 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication.
Arm/Group Title CsA/TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 21 22
Measure Type: Number
Unit of Measure: Percentage of Participants
Death 0 4.5
Graft Loss 0 4.5
Acute Rejection (BPAR) 0 0
4.Secondary Outcome
Title Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months
Hide Description [Not Specified]
Time Frame 12 months, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
Arm/Group Title CsA-TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 21 22
Measure Type: Number
Unit of Measure: participants
12 months 0 0
24 months 0 1
5.Secondary Outcome
Title Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups
Hide Description

GFR Month 9 value if available, otherwise minimal first year post-randomization available value. Imputation rule of missing Month 24 GFR values: GFR Month 18 value if available, otherwise Month 12 GFR is used.

Least square means are from an ANCOVA model containing treatment as factor and baseline eGFR as a covariate.

Time Frame 12 months, 24 months/EOS
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
Arm/Group Title CsA-TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 21 22
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73^2
12 Months (n=21, 22) 62.2  (2.95) 65.6  (2.88)
24 months (n=20, 18) 65.5  (2.51) 71.6  (2.65)
6.Secondary Outcome
Title Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation)
Hide Description Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite
Time Frame baseline, 12 months, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
Arm/Group Title CsA-TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 18 14
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Baseline (n= 18, 14) 1.8  (1.04) 2.4  (.93)
Month 12 (n = 18, 14) 1.9  (1.02) 1.9  (1.00)
Month 24 (n = 8, 5) 2.1  (0.35) 2.0  (0.71)
7.Secondary Outcome
Title Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry
Hide Description

The Fibrosure test is the combination of Fibro-test + Acti-test.

FibroTest (FT) was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase (GGT). FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and >= 0.59 is cirrhosis.

Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase (ALT). ActiTest (AT) was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and >= 0.61 indicates severe necrosis

If 12-month Actitest value was the last available assessment, the value is used to impute the final staging score(End of Study)

Time Frame baseline, 12 and 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.
Arm/Group Title Standard Treatment - Summary of Actitest by Treatment Everolimus -Summary of Actitest by Treatment Standard Treatment -Summary of Fibrotest by Treatment Everolimus - Summary of Fibrotest by Treatment
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 21 22 21 21
Median (Full Range)
Unit of Measure: units on a scale
Baseline (n=21,21,21,21)
0.40
(0.10 to 0.90)
0.50
(0.20 to 1.0)
0.80
(0.40 to 1.0)
0.80
(0.50 to 1.0)
month 12 (n=20,17, 20, 17)
0.60
(0.0 to 0.90)
0.50
(0.20 to 1.0)
0.80
(0.40 to 1.0)
0.80
(0.40 to 1.0)
month 24 (n=1,2,1,2)
0.60
(0.60 to 0.60)
0.70
(0.40 to 0.90)
0.90
(0.90 to 0.90)
1.0
(0.90 to 1.0)
end of study [month 24] (n=20,21,20,21)
0.60
(0.10 to 0.90)
0.50
(0.10 to 1.0)
0.80
(0.50 to 1.0)
0.70
(0.50 to 1.0)
8.Secondary Outcome
Title Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis
Hide Description Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite.
Time Frame baseline to month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Difference Ishak-Knodell Score at End-of-Study The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication
Arm/Group Title Standard Treatment Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 21 22
Measure Type: Number
Unit of Measure: percentage of participants
38.9 7.1
9.Secondary Outcome
Title Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization
Hide Description End of Study (EOS) endpoint is the last available assessment on or after Month 12. A reduction of at least two logs in HCV RNA viral load was considered as success
Time Frame baseline, 12 months, 24 months/EOS
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. If 12-month HCV was the last available assessment, this value is used to impute the End of Study value.
Arm/Group Title CsA-TAC Everolimus
Hide Arm/Group Description:
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: log10 copies/ml
baseline 6.6  (0.69) 6.4  (0.94)
12 months (n=20, 20) 6.5  (0.84) 6.6  (.85)
24 months/EoS (n=20, 20) 6.9  (0.69) 6.7  (0.87)
Month 12 - baseline (n=20,20) -0.1  (0.71) 0.2  (0.72)
Monh 24 - baseline (n=20,20) 0.3  (0.76) 0.3  (0.84)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CsA/TAC EVR (Everolimus)
Hide Arm/Group Description Continuation of current immunosuppressive regimen (continuation of CNI with or without MPA, with or without steroids) / no everolimus introduction. Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
All-Cause Mortality
CsA/TAC EVR (Everolimus)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
CsA/TAC EVR (Everolimus)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)   11/22 (50.00%) 
Cardiac disorders     
Cardio-respiratory arrest  1  0/21 (0.00%)  1/22 (4.55%) 
Tachyarrhythmia  1  0/21 (0.00%)  1/22 (4.55%) 
Gastrointestinal disorders     
Abdominal hernia  1  0/21 (0.00%)  1/22 (4.55%) 
Ascites  1  0/21 (0.00%)  1/22 (4.55%) 
Hepatobiliary disorders     
Cholangitis  1  0/21 (0.00%)  1/22 (4.55%) 
Infections and infestations     
Gastroenteritis  1  0/21 (0.00%)  1/22 (4.55%) 
Hepatitis C  1  0/21 (0.00%)  1/22 (4.55%) 
Pneumonia  1  0/21 (0.00%)  1/22 (4.55%) 
Sepsis  1  0/21 (0.00%)  1/22 (4.55%) 
Wound infection  1  0/21 (0.00%)  1/22 (4.55%) 
Injury, poisoning and procedural complications     
Hepatic haematoma  1  0/21 (0.00%)  1/22 (4.55%) 
Investigations     
Transaminases increased  1  0/21 (0.00%)  1/22 (4.55%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain  1  0/21 (0.00%)  1/22 (4.55%) 
Nervous system disorders     
Ischaemic stroke  1  0/21 (0.00%)  1/22 (4.55%) 
Renal and urinary disorders     
Renal failure  1  0/21 (0.00%)  1/22 (4.55%) 
Reproductive system and breast disorders     
Erectile dysfunction  1  0/21 (0.00%)  1/22 (4.55%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/21 (0.00%)  1/22 (4.55%) 
Pneumonitis  1  0/21 (0.00%)  1/22 (4.55%) 
Respiratory tract congestion  1  0/21 (0.00%)  1/22 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CsA/TAC EVR (Everolimus)
Affected / at Risk (%) Affected / at Risk (%)
Total   8/21 (38.10%)   20/22 (90.91%) 
Blood and lymphatic system disorders     
Leukopenia  1  1/21 (4.76%)  2/22 (9.09%) 
Gastrointestinal disorders     
Aphthous stomatitis  1  0/21 (0.00%)  4/22 (18.18%) 
Diarrhoea  1  0/21 (0.00%)  4/22 (18.18%) 
Mouth ulceration  1  1/21 (4.76%)  2/22 (9.09%) 
Stomatitis  1  0/21 (0.00%)  2/22 (9.09%) 
General disorders     
Pyrexia  1  0/21 (0.00%)  3/22 (13.64%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/21 (0.00%)  2/22 (9.09%) 
Infections and infestations     
Bronchitis  1  0/21 (0.00%)  2/22 (9.09%) 
Influenza  1  1/21 (4.76%)  2/22 (9.09%) 
Upper respiratory tract infection  1  0/21 (0.00%)  2/22 (9.09%) 
Investigations     
Blood cholesterol increased  1  2/21 (9.52%)  3/22 (13.64%) 
Blood triglycerides increased  1  2/21 (9.52%)  1/22 (4.55%) 
Blood uric acid abnormal  1  2/21 (9.52%)  0/22 (0.00%) 
Blood uric acid increased  1  2/21 (9.52%)  0/22 (0.00%) 
Liver function test abnormal  1  0/21 (0.00%)  4/22 (18.18%) 
Platelet count decreased  1  0/21 (0.00%)  3/22 (13.64%) 
Metabolism and nutrition disorders     
Dyslipidaemia  1  0/21 (0.00%)  3/22 (13.64%) 
Hyperglycaemia  1  2/21 (9.52%)  3/22 (13.64%) 
Hypertriglyceridaemia  1  2/21 (9.52%)  3/22 (13.64%) 
Renal and urinary disorders     
Proteinuria  1  2/21 (9.52%)  2/22 (9.09%) 
Renal impairment  1  4/21 (19.05%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders     
Erythema  1  0/21 (0.00%)  3/22 (13.64%) 
Pruritus  1  1/21 (4.76%)  5/22 (22.73%) 
Vascular disorders     
Hypertension  1  1/21 (4.76%)  2/22 (9.09%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Novartis
Organization: Pharmaceuticals
Phone: 41613241111
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00582738     History of Changes
Other Study ID Numbers: CRAD001H2301
First Submitted: December 12, 2007
First Posted: December 28, 2007
Results First Submitted: January 10, 2012
Results First Posted: September 6, 2012
Last Update Posted: September 6, 2012