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A Study to Evaluate the Efficiency of Intravenously Administered Cyclosporine in de Novo Liver Transplant Recipients

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: NCT00332462
Recruitment Status : Completed
First Posted : June 1, 2006
Results First Posted : January 11, 2011
Last Update Posted : March 7, 2011
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Liver Transplantation
Interventions Drug: Cyclosporine (Sandimmun® i.v.)
Drug: Cyclosporine (Sandimmun® Optoral)
Enrollment 34
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cyclosporine (Sandimmun®)
Hide Arm/Group Description Period 1: Cyclosporine (Sandimmun® i.v.) intravenous given 2 times daily as an infusion over four hours staring at a dose of 2 X 200 mg/day for 7 days followed by Period 2: Sandimmun® Optoral microemulsion oral capsule twice daily starting at an initial daily dose of 8-12 mg/kg/day. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels.
Period Title: Overall Study
Started 34 [1]
Patients Treated With Sandimmun® i.v. 34
Patients Treated With Sandimmun® Optoral 29
Completed 18
Not Completed 16
Reason Not Completed
Adverse Event             5
Abnormal Lab Value             1
Unsatisfactory therapeutic effect             4
no longer requires study drug             1
Death             3
Graft Loss             2
[1]
Safety and Intention to treat population.
Arm/Group Title Cyclosporine (Sandimmun®)
Hide Arm/Group Description Period 1: Cyclosporine (Sandimmun® i.v.) intravenous given 2 times daily as an infusion over four hours staring at a dose of 2 X 200 mg/day for 7 days followed by Period 2: Sandimmun® Optoral microemulsion oral capsule twice daily starting at an initial daily dose of 8-12 mg/kg/day. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels.
Overall Number of Baseline Participants 34
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants
53.2  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Female
12
  35.3%
Male
22
  64.7%
1.Primary Outcome
Title Incidence of Biopsy Proven Acute Rejection During the First 3 Months Post de Novo Liver Transplantation
Hide Description Number of patients with biopsy proven acute rejection (BPAR) within 3 months after post de novo liver transplantation. In all suspected rejection episodes an allograft biopsy was performed within a 48 hour period of initiation of an anti-rejection therapy. A designated pathologist graded the biopsies according to the Banff criteria into mild, moderate or severe BPAR.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT) population
Arm/Group Title Cyclosporine (Sandimmun®)
Hide Arm/Group Description:
Period 1: Cyclosporine (Sandimmun® i.v.) intravenous given 2 times daily as an infusion over four hours staring at a dose of 2 X 200 mg/day for 7 days followed by Period 2: Sandimmun® Optoral microemulsion oral capsule twice daily starting at an initial daily dose of 8-12 mg/kg/day. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels.
Overall Number of Participants Analyzed 34
Measure Type: Number
Unit of Measure: Participants
patients with BPAR within 3 months after Tx : YES 8
patients with BPAR within 3 months after Tx : NO 26
2.Secondary Outcome
Title Incidence, Safety and Tolerability of Cyclosporine Intravenous (i.v.) During 6 Months Post de Novo Liver Transplantation
Hide Description The secondary efficacy endpoints included: the incidence of BPAR at 6 months; the incidence of treated acute rejection (TAR) / steroid-resistant acute rejection at 3 and 6 months; the incidence of BPAR with moderate/severe histological grading at 3 and 6 months; time to the first BPAR, the first TAR / steroid-resistant acute rejection and BPAR with moderate/severe histological grading; patient death at 3 and 6 months; and graft loss at 3 and 6 months.
Time Frame 3 or 6 months after transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population.
Arm/Group Title 3 Months After Transplantation 6 Months After Transplantation
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 34 34
Measure Type: Number
Unit of Measure: Participants
Patients with BPAR : YES NA [1]  10
Patients with BPAR : NO NA [1]  24
Patients with TAR : YES 7 8
Patients with TAR : NO 27 26
Patients w/ steroid-resistant acute rejection:YES 2 3
Patients w/ steroid-resistant acute rejection:NO 32 31
BPAR w/ moderate/severe histological grading:YES 4 4
BPAR w/ moderate/severe histological grading:NO 30 30
Occurence of Death : YES 3 3
Occurence of Death : NO 31 31
Occurence of Graft loss : YES 3 3
Occurence of Graft loss : NO 31 31
[1]
analysis was done for 6 month only
Time Frame [Not Specified]
Adverse Event Reporting Description 34 of the 34 study participants received treatment with Cyclosporine (Sandimmun® i.v.). Only 29 of the 34 participants received treatment with Cyclosporine (Sandimmun® Optoral).
 
Arm/Group Title Cyclosporine (Sandimmun® i.v.) Cyclosporine (Sandimmun® Optoral)
Hide Arm/Group Description Cyclosporine (Sandimmun®) intravenous (i.v) given 2 times daily as an infusion over a four hour period staring at a dose of 2 X 200 mg/day and continuing for 7 days. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels. Sandimmun® Optoral microemulsion oral capsule twice daily starting at an initial daily dose of 8-12 mg/kg/day. Dosages were adjusted based on blood levels at two hours to achieve protocol specified target levels.
All-Cause Mortality
Cyclosporine (Sandimmun® i.v.) Cyclosporine (Sandimmun® Optoral)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cyclosporine (Sandimmun® i.v.) Cyclosporine (Sandimmun® Optoral)
Affected / at Risk (%) Affected / at Risk (%)
Total   18/34 (52.94%)   14/29 (48.28%) 
Blood and lymphatic system disorders     
ANAEMIA  1  0/34 (0.00%)  1/29 (3.45%) 
Cardiac disorders     
ATRIAL FLUTTER  1  0/34 (0.00%)  1/29 (3.45%) 
CARDIAC ARREST  1  1/34 (2.94%)  0/29 (0.00%) 
CARDIAC FAILURE  1  1/34 (2.94%)  0/29 (0.00%) 
Gastrointestinal disorders     
ASCITES  1  0/34 (0.00%)  2/29 (6.90%) 
PERITONEAL HAEMATOMA  1  1/34 (2.94%)  0/29 (0.00%) 
General disorders     
HERNIA  1  0/34 (0.00%)  1/29 (3.45%) 
MULTI-ORGAN FAILURE  1  1/34 (2.94%)  0/29 (0.00%) 
SYSTEMIC LEAKAGE  1  0/34 (0.00%)  1/29 (3.45%) 
Hepatobiliary disorders     
BILE DUCT OBSTRUCTION  1  0/34 (0.00%)  1/29 (3.45%) 
BILE DUCT STENOSIS  1  0/34 (0.00%)  1/29 (3.45%) 
BILIARY ISCHAEMIA  1  0/34 (0.00%)  2/29 (6.90%) 
CHOLANGITIS  1  0/34 (0.00%)  3/29 (10.34%) 
CHOLANGITIS SCLEROSING  1  0/34 (0.00%)  1/29 (3.45%) 
Immune system disorders     
GRAFT VERSUS HOST DISEASE  1  0/34 (0.00%)  1/29 (3.45%) 
LIVER TRANSPLANT REJECTION  1  0/34 (0.00%)  1/29 (3.45%) 
Infections and infestations     
CYTOMEGALOVIRUS COLITIS  1  0/34 (0.00%)  1/29 (3.45%) 
CYTOMEGALOVIRUS INFECTION  1  1/34 (2.94%)  0/29 (0.00%) 
DIARRHOEA INFECTIOUS  1  0/34 (0.00%)  1/29 (3.45%) 
GASTROINTESTINAL INFECTION  1  0/34 (0.00%)  1/29 (3.45%) 
HEPATITIS B  1  0/34 (0.00%)  1/29 (3.45%) 
INFECTION  1  0/34 (0.00%)  2/29 (6.90%) 
PNEUMONIA  1  1/34 (2.94%)  1/29 (3.45%) 
SEPSIS  1  1/34 (2.94%)  0/29 (0.00%) 
Injury, poisoning and procedural complications     
ABDOMINAL WOUND DEHISCENCE  1  0/34 (0.00%)  1/29 (3.45%) 
COMPLICATIONS OF TRANSPLANTED LIVER  1  2/34 (5.88%)  1/29 (3.45%) 
HEPATIC HAEMATOMA  1  1/34 (2.94%)  0/29 (0.00%) 
INCISIONAL HERNIA  1  0/34 (0.00%)  1/29 (3.45%) 
POST PROCEDURAL HAEMORRHAGE  1  2/34 (5.88%)  1/29 (3.45%) 
SEROMA  1  0/34 (0.00%)  1/29 (3.45%) 
Investigations     
FIBRINOLYSIS INCREASED  1  1/34 (2.94%)  0/29 (0.00%) 
HEPATIC ENZYME INCREASED  1  0/34 (0.00%)  1/29 (3.45%) 
HEPATITIS C VIRUS  1  0/34 (0.00%)  1/29 (3.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
NEUROENDOCRINE TUMOUR  1  0/34 (0.00%)  1/29 (3.45%) 
Nervous system disorders     
ENCEPHALOPATHY  1  1/34 (2.94%)  0/29 (0.00%) 
Renal and urinary disorders     
ANURIA  1  1/34 (2.94%)  0/29 (0.00%) 
RENAL FAILURE  1  2/34 (5.88%)  2/29 (6.90%) 
RENAL FAILURE ACUTE  1  2/34 (5.88%)  0/29 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
RESPIRATORY FAILURE  1  3/34 (8.82%)  1/29 (3.45%) 
Vascular disorders     
HAEMORRHAGE  1  5/34 (14.71%)  0/29 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cyclosporine (Sandimmun® i.v.) Cyclosporine (Sandimmun® Optoral)
Affected / at Risk (%) Affected / at Risk (%)
Total   34/34 (100.00%)   29/29 (100.00%) 
Blood and lymphatic system disorders     
ANAEMIA  1  18/34 (52.94%)  10/29 (34.48%) 
COAGULOPATHY  1  12/34 (35.29%)  1/29 (3.45%) 
LEUKOCYTOSIS  1  2/34 (5.88%)  0/29 (0.00%) 
LEUKOPENIA  1  1/34 (2.94%)  4/29 (13.79%) 
NEUTROPENIA  1  1/34 (2.94%)  2/29 (6.90%) 
THROMBOCYTOPENIA  1  10/34 (29.41%)  2/29 (6.90%) 
Cardiac disorders     
ARRHYTHMIA  1  2/34 (5.88%)  0/29 (0.00%) 
BRADYCARDIA  1  5/34 (14.71%)  1/29 (3.45%) 
TACHYARRHYTHMIA  1  4/34 (11.76%)  0/29 (0.00%) 
Congenital, familial and genetic disorders     
ANTITHROMBIN III DEFICIENCY  1  8/34 (23.53%)  0/29 (0.00%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  4/34 (11.76%)  8/29 (27.59%) 
ASCITES  1  2/34 (5.88%)  4/29 (13.79%) 
CONSTIPATION  1  15/34 (44.12%)  7/29 (24.14%) 
DIARRHOEA  1  2/34 (5.88%)  7/29 (24.14%) 
FLATULENCE  1  4/34 (11.76%)  3/29 (10.34%) 
NAUSEA  1  2/34 (5.88%)  2/29 (6.90%) 
PERITONITIS  1  0/34 (0.00%)  2/29 (6.90%) 
VOMITING  1  4/34 (11.76%)  4/29 (13.79%) 
General disorders     
IMPAIRED HEALING  1  0/34 (0.00%)  5/29 (17.24%) 
MALAISE  1  2/34 (5.88%)  1/29 (3.45%) 
OEDEMA  1  3/34 (8.82%)  5/29 (17.24%) 
OEDEMA PERIPHERAL  1  0/34 (0.00%)  7/29 (24.14%) 
PUNCTURE SITE PAIN  1  0/34 (0.00%)  3/29 (10.34%) 
PYREXIA  1  4/34 (11.76%)  8/29 (27.59%) 
Hepatobiliary disorders     
CHOLANGITIS  1  2/34 (5.88%)  7/29 (24.14%) 
CHOLESTASIS  1  20/34 (58.82%)  10/29 (34.48%) 
Infections and infestations     
ABDOMINAL INFECTION  1  0/34 (0.00%)  2/29 (6.90%) 
CANDIDIASIS  1  1/34 (2.94%)  2/29 (6.90%) 
CYTOMEGALOVIRUS INFECTION  1  1/34 (2.94%)  5/29 (17.24%) 
FUNGAL INFECTION  1  0/34 (0.00%)  2/29 (6.90%) 
HERPES SIMPLEX  1  1/34 (2.94%)  2/29 (6.90%) 
INFECTION  1  5/34 (14.71%)  2/29 (6.90%) 
PHARYNGITIS  1  1/34 (2.94%)  2/29 (6.90%) 
PNEUMONIA  1  2/34 (5.88%)  1/29 (3.45%) 
SEPSIS  1  3/34 (8.82%)  0/29 (0.00%) 
SYSTEMIC CANDIDA  1  0/34 (0.00%)  2/29 (6.90%) 
URINARY TRACT INFECTION  1  3/34 (8.82%)  5/29 (17.24%) 
WOUND INFECTION  1  1/34 (2.94%)  5/29 (17.24%) 
Injury, poisoning and procedural complications     
ANAEMIA POSTOPERATIVE  1  2/34 (5.88%)  0/29 (0.00%) 
COMPLICATIONS OF TRANSPLANTED LIVER  1  3/34 (8.82%)  1/29 (3.45%) 
OPERATIVE HAEMORRHAGE  1  5/34 (14.71%)  0/29 (0.00%) 
PROCEDURAL HYPOTENSION  1  3/34 (8.82%)  0/29 (0.00%) 
PROCEDURAL PAIN  1  17/34 (50.00%)  2/29 (6.90%) 
WOUND COMPLICATION  1  2/34 (5.88%)  4/29 (13.79%) 
Investigations     
C-REACTIVE PROTEIN INCREASED  1  0/34 (0.00%)  2/29 (6.90%) 
TRANSAMINASES INCREASED  1  1/34 (2.94%)  3/29 (10.34%) 
Metabolism and nutrition disorders     
DIABETES MELLITUS  1  1/34 (2.94%)  2/29 (6.90%) 
FOLATE DEFICIENCY  1  0/34 (0.00%)  2/29 (6.90%) 
HYPERGLYCAEMIA  1  17/34 (50.00%)  2/29 (6.90%) 
HYPERKALAEMIA  1  6/34 (17.65%)  2/29 (6.90%) 
HYPERNATRAEMIA  1  2/34 (5.88%)  0/29 (0.00%) 
HYPERPHOSPHATAEMIA  1  0/34 (0.00%)  3/29 (10.34%) 
HYPOALBUMINAEMIA  1  15/34 (44.12%)  3/29 (10.34%) 
HYPOCALCAEMIA  1  8/34 (23.53%)  10/29 (34.48%) 
HYPOGLYCAEMIA  1  3/34 (8.82%)  0/29 (0.00%) 
HYPOKALAEMIA  1  11/34 (32.35%)  2/29 (6.90%) 
HYPOMAGNESAEMIA  1  1/34 (2.94%)  5/29 (17.24%) 
METABOLIC ACIDOSIS  1  10/34 (29.41%)  0/29 (0.00%) 
VITAMIN K DEFICIENCY  1  0/34 (0.00%)  2/29 (6.90%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  0/34 (0.00%)  2/29 (6.90%) 
BACK PAIN  1  1/34 (2.94%)  5/29 (17.24%) 
MYALGIA  1  0/34 (0.00%)  2/29 (6.90%) 
Nervous system disorders     
HEADACHE  1  0/34 (0.00%)  2/29 (6.90%) 
Psychiatric disorders     
DEPRESSION  1  2/34 (5.88%)  4/29 (13.79%) 
INSOMNIA  1  13/34 (38.24%)  8/29 (27.59%) 
PSYCHOTIC DISORDER  1  4/34 (11.76%)  0/29 (0.00%) 
SLEEP DISORDER  1  4/34 (11.76%)  0/29 (0.00%) 
Renal and urinary disorders     
OLIGURIA  1  5/34 (14.71%)  0/29 (0.00%) 
RENAL FAILURE  1  18/34 (52.94%)  7/29 (24.14%) 
Respiratory, thoracic and mediastinal disorders     
BRONCHOSPASM  1  7/34 (20.59%)  1/29 (3.45%) 
COUGH  1  0/34 (0.00%)  2/29 (6.90%) 
EPISTAXIS  1  2/34 (5.88%)  1/29 (3.45%) 
PLEURAL EFFUSION  1  16/34 (47.06%)  4/29 (13.79%) 
RESPIRATORY FAILURE  1  6/34 (17.65%)  1/29 (3.45%) 
Skin and subcutaneous tissue disorders     
DECUBITUS ULCER  1  3/34 (8.82%)  1/29 (3.45%) 
SCAR PAIN  1  0/34 (0.00%)  3/29 (10.34%) 
Vascular disorders     
HAEMATOMA  1  2/34 (5.88%)  0/29 (0.00%) 
HYPERTENSION  1  11/34 (32.35%)  7/29 (24.14%) 
HYPOTENSION  1  17/34 (50.00%)  4/29 (13.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
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
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00332462     History of Changes
Other Study ID Numbers: COLO400ADE01
First Submitted: May 30, 2006
First Posted: June 1, 2006
Results First Submitted: December 13, 2010
Results First Posted: January 11, 2011
Last Update Posted: March 7, 2011