Trial Outcomes & Findings for RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency (NCT NCT00267189)
NCT ID: NCT00267189
Last Updated: 2011-04-13
Results Overview
The primary variable was renal function assessed by calculated creatinine clearance using the Cockcroft-Gault formula, and was assessed at all visits. CrCl\[mL/min\] = (140 - A) \* W / (72 \* C) \* R. Where A is age at sample date \[years\], W is body weight at specific visit \[kg\], C is the serum concentration of creatinine \[mg/dL\], R = 1 if the patient is male and = 0.85 if female.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
145 participants
Primary outcome timeframe
From baseline to 6 months
Results posted on
2011-04-13
Participant Flow
Participant milestones
| Measure |
Group 1 (Everolimus)
Reduced or discontinued CNI dose + everolimus (3-12 ng/mL) ± steroids
|
Group 2 (Control)
Standard CNI dose ± mycophenolate acid (MPA)/azathioprine (AZA) ± steroids
|
|---|---|---|
|
Overall Study
STARTED
|
72
|
73
|
|
Overall Study
Completed Study Medication
|
54
|
72
|
|
Overall Study
COMPLETED
|
67
|
72
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
| Measure |
Group 1 (Everolimus)
Reduced or discontinued CNI dose + everolimus (3-12 ng/mL) ± steroids
|
Group 2 (Control)
Standard CNI dose ± mycophenolate acid (MPA)/azathioprine (AZA) ± steroids
|
|---|---|---|
|
Overall Study
Patient withdrew consent
|
1
|
1
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Missing
|
3
|
0
|
Baseline Characteristics
RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency
Baseline characteristics by cohort
| Measure |
Group 1 (Everolimus)
n=72 Participants
Reduced or discontinued CNI dose + everolimus (3-12 ng/mL) ± steroids
|
Group 2 (Control)
n=73 Participants
Standard CNI dose ± mycophenolate acid (MPA)/azathioprine (AZA) ± steroids
|
Total
n=145 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
57.0 Years
STANDARD_DEVIATION 8.45 • n=99 Participants
|
57.8 Years
STANDARD_DEVIATION 6.93 • n=107 Participants
|
57.4 Years
STANDARD_DEVIATION 7.70 • n=206 Participants
|
|
Age, Customized
< 40 years
|
1 Paricipants
n=99 Participants
|
2 Paricipants
n=107 Participants
|
3 Paricipants
n=206 Participants
|
|
Age, Customized
>= 40 - < 50 years
|
12 Paricipants
n=99 Participants
|
7 Paricipants
n=107 Participants
|
19 Paricipants
n=206 Participants
|
|
Age, Customized
>= 50 - < 60 years
|
29 Paricipants
n=99 Participants
|
33 Paricipants
n=107 Participants
|
62 Paricipants
n=206 Participants
|
|
Age, Customized
>= 60 years
|
30 Paricipants
n=99 Participants
|
31 Paricipants
n=107 Participants
|
61 Paricipants
n=206 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
60 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=99 Participants
|
40 Participants
n=107 Participants
|
85 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: From baseline to 6 monthsPopulation: Intention to treat (ITT) population includes all patients who were randomized to one of the treatment groups and received at least one dose of study medication. Patients with baseline and 6 month creatinine clearance were included in analysis. Missing values at 6 months were imputed using the last observation carried forward (LOCF) approach.
The primary variable was renal function assessed by calculated creatinine clearance using the Cockcroft-Gault formula, and was assessed at all visits. CrCl\[mL/min\] = (140 - A) \* W / (72 \* C) \* R. Where A is age at sample date \[years\], W is body weight at specific visit \[kg\], C is the serum concentration of creatinine \[mg/dL\], R = 1 if the patient is male and = 0.85 if female.
Outcome measures
| Measure |
Group 1 (Everolimus)
n=71 Participants
Reduced or discontinued CNI dose + everolimus (3-12 ng/mL) ± steroids
|
Group 2 (Control)
n=71 Participants
Standard CNI dose ± mycophenolate acid (MPA)/azathioprine (AZA) ± steroids
|
|---|---|---|
|
Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl)
|
0.99 mL/min
Standard Deviation 10.25
|
2.26 mL/min
Standard Deviation 7.79
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Intention to treat (ITT) population includes all patients who were randomized to one of the treatment groups and received at least one dose of study medication.
The composite efficacy failure endpoint encompasses at least one of: biopsy proven acute rejection, graft loss, or death for the patient. BPAR was defined as a clinically suspected acute rejection confirmed by biopsy. Acute rejection episodes were recorded as Liver Allograft Rejection. The allograft was presumed to be lost if a patient had a liver retransplant or died.
Outcome measures
| Measure |
Group 1 (Everolimus)
n=72 Participants
Reduced or discontinued CNI dose + everolimus (3-12 ng/mL) ± steroids
|
Group 2 (Control)
n=73 Participants
Standard CNI dose ± mycophenolate acid (MPA)/azathioprine (AZA) ± steroids
|
|---|---|---|
|
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
Composite efficacy failure (total)
|
2.8 Percentage of patients
|
1.4 Percentage of patients
|
|
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
Biopsy proven acute rejection
|
1.4 Percentage of patients
|
1.4 Percentage of patients
|
|
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
Graft Loss
|
0 Percentage of patients
|
0 Percentage of patients
|
|
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
Death
|
1.4 Percentage of patients
|
0 Percentage of patients
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Intention to treat (ITT) population includes all patients who were randomized to one of the treatment groups and received at least one dose of study medication.
Outcome measures
| Measure |
Group 1 (Everolimus)
n=72 Participants
Reduced or discontinued CNI dose + everolimus (3-12 ng/mL) ± steroids
|
Group 2 (Control)
n=73 Participants
Standard CNI dose ± mycophenolate acid (MPA)/azathioprine (AZA) ± steroids
|
|---|---|---|
|
Number of Patients With Discontinuation of Study Medication
Patient withdrew consent
|
2 Patients
|
1 Patients
|
|
Number of Patients With Discontinuation of Study Medication
Abnormal laboratory value(s)
|
1 Patients
|
0 Patients
|
|
Number of Patients With Discontinuation of Study Medication
Total # of discontinuation of study medication
|
18 Patients
|
1 Patients
|
|
Number of Patients With Discontinuation of Study Medication
Adverse Event
|
14 Patients
|
0 Patients
|
|
Number of Patients With Discontinuation of Study Medication
Administrative problems
|
1 Patients
|
0 Patients
|
Adverse Events
Group 1 (Everolimus)
Serious events: 18 serious events
Other events: 58 other events
Deaths: 0 deaths
Group 2 (Control)
Serious events: 14 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1 (Everolimus)
n=72 participants at risk
Reduced calcineurin inhibitor dose + everolimus (1.5 mg twice daily) ± steroids
|
Group 2 (Control)
n=73 participants at risk
Standard calcineurin inhibitor dose ± mycophenolate acid/azathioprine ± steroids
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.4%
1/72
|
2.7%
2/73
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/72
|
1.4%
1/73
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.4%
1/72
|
1.4%
1/73
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/72
|
1.4%
1/73
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/72
|
1.4%
1/73
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
1.4%
1/72
|
0.00%
0/73
|
|
Cardiac disorders
Arrhythmia
|
1.4%
1/72
|
0.00%
0/73
|
|
Cardiac disorders
Cardiac failure
|
1.4%
1/72
|
0.00%
0/73
|
|
Cardiac disorders
Myocardial infarction
|
1.4%
1/72
|
0.00%
0/73
|
|
Eye disorders
Diplopia
|
1.4%
1/72
|
0.00%
0/73
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
1/72
|
1.4%
1/73
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.00%
0/72
|
1.4%
1/73
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/72
|
1.4%
1/73
|
|
Gastrointestinal disorders
Umbilical hernia
|
1.4%
1/72
|
0.00%
0/73
|
|
Gastrointestinal disorders
Vomiting
|
1.4%
1/72
|
0.00%
0/73
|
|
General disorders
Hyperpyrexia
|
2.8%
2/72
|
0.00%
0/73
|
|
General disorders
Inflammation
|
0.00%
0/72
|
1.4%
1/73
|
|
General disorders
Influenza like illness
|
0.00%
0/72
|
1.4%
1/73
|
|
General disorders
Pyrexia
|
1.4%
1/72
|
2.7%
2/73
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/72
|
1.4%
1/73
|
|
Hepatobiliary disorders
Cytolytic hepatitis
|
1.4%
1/72
|
0.00%
0/73
|
|
Immune system disorders
Liver transplant rejection
|
1.4%
1/72
|
0.00%
0/73
|
|
Infections and infestations
Cytomegalovirus infection
|
1.4%
1/72
|
0.00%
0/73
|
|
Infections and infestations
Gastroenteritis
|
1.4%
1/72
|
1.4%
1/73
|
|
Infections and infestations
Septic shock
|
1.4%
1/72
|
0.00%
0/73
|
|
Infections and infestations
Urinary tract infection
|
1.4%
1/72
|
0.00%
0/73
|
|
Injury, poisoning and procedural complications
Contusion
|
1.4%
1/72
|
0.00%
0/73
|
|
Injury, poisoning and procedural complications
Overdose
|
1.4%
1/72
|
0.00%
0/73
|
|
Injury, poisoning and procedural complications
Traumatic shock
|
0.00%
0/72
|
1.4%
1/73
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.4%
1/72
|
0.00%
0/73
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/72
|
1.4%
1/73
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.4%
1/72
|
0.00%
0/73
|
|
Nervous system disorders
Headache
|
1.4%
1/72
|
0.00%
0/73
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/72
|
1.4%
1/73
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/72
|
1.4%
1/73
|
|
Renal and urinary disorders
Renal failure acute
|
1.4%
1/72
|
0.00%
0/73
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/72
|
1.4%
1/73
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.8%
2/72
|
1.4%
1/73
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.4%
1/72
|
0.00%
0/73
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
1.4%
1/72
|
0.00%
0/73
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
1.4%
1/72
|
0.00%
0/73
|
|
Skin and subcutaneous tissue disorders
Skin erosion
|
1.4%
1/72
|
0.00%
0/73
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
1.4%
1/72
|
0.00%
0/73
|
|
Vascular disorders
Arteritis
|
0.00%
0/72
|
1.4%
1/73
|
|
Vascular disorders
Phlebitis
|
1.4%
1/72
|
0.00%
0/73
|
Other adverse events
| Measure |
Group 1 (Everolimus)
n=72 participants at risk
Reduced calcineurin inhibitor dose + everolimus (1.5 mg twice daily) ± steroids
|
Group 2 (Control)
n=73 participants at risk
Standard calcineurin inhibitor dose ± mycophenolate acid/azathioprine ± steroids
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
6/72
|
2.7%
2/73
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.1%
8/72
|
4.1%
3/73
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
4/72
|
0.00%
0/73
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
15.3%
11/72
|
0.00%
0/73
|
|
Gastrointestinal disorders
Diarrhoea
|
9.7%
7/72
|
2.7%
2/73
|
|
Gastrointestinal disorders
Dyspepsia
|
5.6%
4/72
|
2.7%
2/73
|
|
Gastrointestinal disorders
Mouth ulceration
|
11.1%
8/72
|
0.00%
0/73
|
|
Gastrointestinal disorders
Nausea
|
8.3%
6/72
|
6.8%
5/73
|
|
General disorders
Asthenia
|
6.9%
5/72
|
1.4%
1/73
|
|
General disorders
Oedema peripheral
|
5.6%
4/72
|
1.4%
1/73
|
|
General disorders
Pyrexia
|
5.6%
4/72
|
4.1%
3/73
|
|
Infections and infestations
Bronchitis
|
5.6%
4/72
|
6.8%
5/73
|
|
Infections and infestations
Herpes simplex
|
8.3%
6/72
|
4.1%
3/73
|
|
Infections and infestations
Nasopharyngitis
|
6.9%
5/72
|
6.8%
5/73
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/72
|
5.5%
4/73
|
|
Investigations
Blood creatine phosphokinase increased
|
5.6%
4/72
|
0.00%
0/73
|
|
Investigations
Hepatitis C virus
|
6.9%
5/72
|
0.00%
0/73
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
13.9%
10/72
|
2.7%
2/73
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
8.3%
6/72
|
4.1%
3/73
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
9.7%
7/72
|
2.7%
2/73
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.9%
5/72
|
1.4%
1/73
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.8%
2/72
|
6.8%
5/73
|
|
Nervous system disorders
Headache
|
8.3%
6/72
|
2.7%
2/73
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/72
|
5.5%
4/73
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
6/72
|
2.7%
2/73
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.9%
5/72
|
0.00%
0/73
|
|
Skin and subcutaneous tissue disorders
Eczema
|
6.9%
5/72
|
0.00%
0/73
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.6%
4/72
|
1.4%
1/73
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.9%
5/72
|
0.00%
0/73
|
|
Vascular disorders
Hypertension
|
4.2%
3/72
|
6.8%
5/73
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
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.
- Publication restrictions are in place
Restriction type: OTHER