Trial Outcomes & Findings for Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C (NCT NCT00938860)
NCT ID: NCT00938860
Last Updated: 2015-05-22
Results Overview
The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
COMPLETED
PHASE4
92 participants
Week 24
2015-05-22
Participant Flow
This was an 80 week multicenter randomized, open label, controlled study in adult HCVpositive maintenance liver transplant recipients. Patients were randomized at a 1.3:1 ratio to CsA and tacrolimus. Patients randomized to tacrolimus were maintained on treatment with tacrolimus, patients randomized to CsA were converted from tacrolimus to CsA
Participant milestones
| Measure |
Neoral
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
42
|
|
Overall Study
Efficacy Population
|
40
|
41
|
|
Overall Study
COMPLETED
|
25
|
25
|
|
Overall Study
NOT COMPLETED
|
25
|
17
|
Reasons for withdrawal
| Measure |
Neoral
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Abnormal laboratory values
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
11
|
8
|
|
Overall Study
Lost to Follow-up
|
4
|
4
|
|
Overall Study
Administration problems
|
2
|
0
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Protocol Violation
|
3
|
1
|
Baseline Characteristics
Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
Baseline characteristics by cohort
| Measure |
Neoral
n=50 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=42 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.2 Years
STANDARD_DEVIATION 6.30 • n=99 Participants
|
55.0 Years
STANDARD_DEVIATION 6.84 • n=107 Participants
|
54.6 Years
STANDARD_DEVIATION 6.53 • n=206 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=99 Participants
|
34 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
Outcome measures
| Measure |
Neoral
n=20 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=23 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus
|
12 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Week 80Population: Intent-to-Treat (ITT) population: The ITT population consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
Efficacy failure (biopsy proven acute rejection (BPAR), graft loss, or death
Outcome measures
| Measure |
Neoral
n=50 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=42 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
BPAR, graft loss, or death
|
2 Number of events
|
1 Number of events
|
|
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
BPAR
|
1 Number of events
|
0 Number of events
|
|
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
Graft loss or death
|
1 Number of events
|
1 Number of events
|
|
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
Death
|
1 Number of events
|
1 Number of events
|
SECONDARY outcome
Timeframe: Week 80Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
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, Participants showing an increase of Ishak Knodell fibrosis score by at least one level (increase of ≥1)
Outcome measures
| Measure |
Neoral
n=13 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=17 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline)
|
3 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Week 4Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
RVR defined as non-detectable HCV RNA 4 weeks after initiation of antiviral treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
Outcome measures
| Measure |
Neoral
n=36 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=38 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants of Rapid Viral Response (RVR)
|
4 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Week 12Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
EVR defined as non-detectable HCV RNA or a ≥2 logs reduction of HCV RNA at 12 weeks after initiation of antiviral treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
Outcome measures
| Measure |
Neoral
n=31 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=36 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants of Early Viral Response (EVR)
|
28 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: Week 80Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
ETR defined as non-detectable HCV RNA at the completion of AV treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
Outcome measures
| Measure |
Neoral
n=35 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=39 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants for the End of Treatment Response (ETR)
|
24 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: Week 80Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
Defined as failure to achieve at least a 2 log reduction of Hepatitis C virus (HCV) RNA. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
Outcome measures
| Measure |
Neoral
n=40 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=41 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants of True Non-responder Rate
|
7 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Week 24Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
Defined as reappearance of detectable Hepatitis C Virus (HCV) RNA at 24 weeks after completion of antiviral treatment when HCV RNA was undetectable at the end of treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)
Outcome measures
| Measure |
Neoral
n=23 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=21 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants for Relapse Rate
|
5 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Week 80Population: The efficacy population was defined as a subset of the ITT population with sufficient compliance to the protocol procedures to allow meaningful conclusions. Patients were excluded from the Efficacy population in case of: Error in treatment assignment, if the randomized study medication was not initiated, antiviral therapy was not initiated
Defined as number of patients with dose reduction or discontinuation of AV therapy due to poor tolerability
Outcome measures
| Measure |
Neoral
n=40 Participants
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
Tacrolimus
n=41 Participants
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
|---|---|---|
|
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Neoral Antiviral treatment: Ribavirin
|
25 Participants
|
0 Participants
|
|
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Neoral Antiviral treatment: Peg-IFN
|
10 Participants
|
0 Participants
|
|
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Tacrolimus Antiviral treatment: Ribavirin
|
0 Participants
|
23 Participants
|
|
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Tacrolimus Antiviral treatment: Peg-IFN
|
0 Participants
|
11 Participants
|
Adverse Events
Tacrolimus
Neoral
Serious adverse events
| Measure |
Tacrolimus
n=42 participants at risk
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
Neoral
n=50 participants at risk
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.9%
5/42
|
12.0%
6/50
|
|
Blood and lymphatic system disorders
Haemolysis
|
2.4%
1/42
|
0.00%
0/50
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
0.00%
0/42
|
2.0%
1/50
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.4%
1/42
|
2.0%
1/50
|
|
Blood and lymphatic system disorders
Pancytopenia
|
2.4%
1/42
|
2.0%
1/50
|
|
Cardiac disorders
Acute myocardial infarction
|
2.4%
1/42
|
0.00%
0/50
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/42
|
2.0%
1/50
|
|
Cardiac disorders
Coronary artery disease
|
2.4%
1/42
|
0.00%
0/50
|
|
Cardiac disorders
Ventricular fibrillation
|
2.4%
1/42
|
0.00%
0/50
|
|
Eye disorders
Exophthalmos
|
2.4%
1/42
|
0.00%
0/50
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/42
|
2.0%
1/50
|
|
Gastrointestinal disorders
Abdominal pain
|
2.4%
1/42
|
4.0%
2/50
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.8%
2/42
|
0.00%
0/50
|
|
Gastrointestinal disorders
Anal fissure
|
2.4%
1/42
|
0.00%
0/50
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/42
|
2.0%
1/50
|
|
Gastrointestinal disorders
Diarrhoea
|
4.8%
2/42
|
0.00%
0/50
|
|
Gastrointestinal disorders
Nausea
|
2.4%
1/42
|
2.0%
1/50
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/42
|
2.0%
1/50
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/42
|
2.0%
1/50
|
|
General disorders
Asthenia
|
2.4%
1/42
|
4.0%
2/50
|
|
General disorders
Fatigue
|
2.4%
1/42
|
0.00%
0/50
|
|
General disorders
Pyrexia
|
7.1%
3/42
|
4.0%
2/50
|
|
Hepatobiliary disorders
Bile duct stenosis
|
2.4%
1/42
|
0.00%
0/50
|
|
Hepatobiliary disorders
Bile duct stone
|
2.4%
1/42
|
0.00%
0/50
|
|
Hepatobiliary disorders
Cholangitis
|
2.4%
1/42
|
2.0%
1/50
|
|
Hepatobiliary disorders
Cholestasis
|
4.8%
2/42
|
0.00%
0/50
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/42
|
2.0%
1/50
|
|
Immune system disorders
Liver transplant rejection
|
0.00%
0/42
|
2.0%
1/50
|
|
Immune system disorders
Transplant rejection
|
0.00%
0/42
|
2.0%
1/50
|
|
Infections and infestations
Clostridium difficile colitis
|
2.4%
1/42
|
0.00%
0/50
|
|
Infections and infestations
Dengue fever
|
0.00%
0/42
|
2.0%
1/50
|
|
Infections and infestations
Enterobacter bacteraemia
|
2.4%
1/42
|
0.00%
0/50
|
|
Infections and infestations
Gastroenteritis
|
2.4%
1/42
|
0.00%
0/50
|
|
Infections and infestations
Hepatitis C
|
0.00%
0/42
|
2.0%
1/50
|
|
Infections and infestations
Pneumonia
|
2.4%
1/42
|
0.00%
0/50
|
|
Infections and infestations
Pyelonephritis
|
2.4%
1/42
|
0.00%
0/50
|
|
Infections and infestations
Pyoderma
|
2.4%
1/42
|
0.00%
0/50
|
|
Infections and infestations
Sepsis
|
2.4%
1/42
|
2.0%
1/50
|
|
Infections and infestations
Septic shock
|
0.00%
0/42
|
2.0%
1/50
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/42
|
2.0%
1/50
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/42
|
6.0%
3/50
|
|
Infections and infestations
Urosepsis
|
0.00%
0/42
|
2.0%
1/50
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
2.4%
1/42
|
0.00%
0/50
|
|
Metabolism and nutrition disorders
Dehydration
|
2.4%
1/42
|
0.00%
0/50
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.4%
1/42
|
0.00%
0/50
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
2.4%
1/42
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis
|
2.4%
1/42
|
0.00%
0/50
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/42
|
2.0%
1/50
|
|
Nervous system disorders
Cerebral haemorrhage
|
2.4%
1/42
|
2.0%
1/50
|
|
Nervous system disorders
Dementia Alzheimer's type
|
0.00%
0/42
|
2.0%
1/50
|
|
Nervous system disorders
Encephalopathy
|
4.8%
2/42
|
2.0%
1/50
|
|
Nervous system disorders
Headache
|
2.4%
1/42
|
0.00%
0/50
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/42
|
2.0%
1/50
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.00%
0/42
|
2.0%
1/50
|
|
Nervous system disorders
Syncope
|
4.8%
2/42
|
0.00%
0/50
|
|
Psychiatric disorders
Adjustment disorder with depressed mood
|
0.00%
0/42
|
2.0%
1/50
|
|
Psychiatric disorders
Drug abuse
|
0.00%
0/42
|
2.0%
1/50
|
|
Renal and urinary disorders
Calculus ureteric
|
2.4%
1/42
|
0.00%
0/50
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/42
|
2.0%
1/50
|
|
Renal and urinary disorders
Renal failure
|
2.4%
1/42
|
0.00%
0/50
|
|
Renal and urinary disorders
Renal failure acute
|
2.4%
1/42
|
2.0%
1/50
|
|
Renal and urinary disorders
Renal impairment
|
2.4%
1/42
|
0.00%
0/50
|
|
Reproductive system and breast disorders
Gynaecomastia
|
2.4%
1/42
|
2.0%
1/50
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/42
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/42
|
2.0%
1/50
|
|
Vascular disorders
Shock
|
2.4%
1/42
|
0.00%
0/50
|
Other adverse events
| Measure |
Tacrolimus
n=42 participants at risk
Prograf® (tacrolimus) provided as 0.5 mg, 1 mg and 5 mg capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals. Doses were adjusted as necessary to achieve and maintain recommended C0 target ranges
|
Neoral
n=50 participants at risk
Neoral® (cyclosporine for microemulsion), available as 10 mg, 25 mg, 50 mg and 100 mg soft gelatin capsules taken on a twice daily (b.i.d) schedule at 12-hour intervals, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
66.7%
28/42
|
54.0%
27/50
|
|
Blood and lymphatic system disorders
Leukopenia
|
21.4%
9/42
|
20.0%
10/50
|
|
Blood and lymphatic system disorders
Neutropenia
|
33.3%
14/42
|
12.0%
6/50
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.5%
4/42
|
8.0%
4/50
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
3/42
|
2.0%
1/50
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.8%
2/42
|
8.0%
4/50
|
|
Gastrointestinal disorders
Constipation
|
4.8%
2/42
|
8.0%
4/50
|
|
Gastrointestinal disorders
Diarrhoea
|
26.2%
11/42
|
18.0%
9/50
|
|
Gastrointestinal disorders
Nausea
|
26.2%
11/42
|
12.0%
6/50
|
|
Gastrointestinal disorders
Stomatitis
|
2.4%
1/42
|
8.0%
4/50
|
|
Gastrointestinal disorders
Vomiting
|
2.4%
1/42
|
6.0%
3/50
|
|
General disorders
Asthenia
|
23.8%
10/42
|
14.0%
7/50
|
|
General disorders
Chills
|
7.1%
3/42
|
4.0%
2/50
|
|
General disorders
Fatigue
|
31.0%
13/42
|
24.0%
12/50
|
|
General disorders
Influenza like illness
|
16.7%
7/42
|
6.0%
3/50
|
|
General disorders
Irritability
|
14.3%
6/42
|
0.00%
0/50
|
|
General disorders
Oedema peripheral
|
4.8%
2/42
|
10.0%
5/50
|
|
General disorders
Pain
|
0.00%
0/42
|
6.0%
3/50
|
|
General disorders
Pyrexia
|
11.9%
5/42
|
16.0%
8/50
|
|
Infections and infestations
Urinary tract infection
|
7.1%
3/42
|
4.0%
2/50
|
|
Investigations
Haemoglobin decreased
|
9.5%
4/42
|
0.00%
0/50
|
|
Investigations
Neutrophil count decreased
|
7.1%
3/42
|
2.0%
1/50
|
|
Investigations
Weight decreased
|
9.5%
4/42
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.9%
5/42
|
10.0%
5/50
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
4.8%
2/42
|
8.0%
4/50
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
3/42
|
6.0%
3/50
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
3/42
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
16.7%
7/42
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.5%
4/42
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.1%
3/42
|
6.0%
3/50
|
|
Nervous system disorders
Dizziness
|
19.0%
8/42
|
8.0%
4/50
|
|
Nervous system disorders
Headache
|
16.7%
7/42
|
16.0%
8/50
|
|
Psychiatric disorders
Anxiety
|
4.8%
2/42
|
6.0%
3/50
|
|
Psychiatric disorders
Depression
|
9.5%
4/42
|
14.0%
7/50
|
|
Psychiatric disorders
Insomnia
|
14.3%
6/42
|
12.0%
6/50
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.5%
4/42
|
12.0%
6/50
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
19.0%
8/42
|
10.0%
5/50
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.1%
3/42
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Eczema
|
4.8%
2/42
|
6.0%
3/50
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.3%
6/42
|
12.0%
6/50
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
9.5%
4/42
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.1%
3/42
|
2.0%
1/50
|
|
Vascular disorders
Hypertension
|
9.5%
4/42
|
18.0%
9/50
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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 or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER