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Trial registered on ANZCTR


Registration number
ACTRN12610000837022
Ethics application status
Approved
Date submitted
14/12/2009
Date registered
6/10/2010
Date last updated
30/06/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and Safety of Alemtuzumab for prevention of graft rejection and preservation of renal function in patients receiving Kidney Transplant
Scientific title
A Randomised Controlled Trial of the Efficacy and Safety of Alemtuzumab (MABCAMPATH) for Prevention of Graft Rejection and Preservation of Renal Function in Patients Receiving Kidney Transplants
Secondary ID [1] 251675 0
nil
Universal Trial Number (UTN)
Trial acronym
CAMP ASIA 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End stage kidney failure 252320 0
Condition category
Condition code
Renal and Urogenital 252506 252506 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For CAMPATH Group, the intervention is administration of 2 doses of alemtuzumab 20 mg intravenously, 1st dose within 6 hours post anastomosis and 2nd dose 24 hours after 1st dose, followed by treatment with low-dose Tacrolimus (oral tablets twice daily for 3 years) adjusted to Trough levels of 5-7 ng/mL for duration of trial. Patients will be followed up for 3 years after transplantation surgery.
Intervention code [1] 255625 0
Treatment: Drugs
Comparator / control treatment
Administration of Tacrolimus in both groups is twice daily. For Campath Group, tacrolimus treatment will be initiated at 0.15 mg/kg twice a day per oral, will be administered a window of 48 hours after the second dose of alemtuzumab 20 mg intravenously. Subsequently, the tacrolimus dose will be lower to 0.1 mg/kg twice a day per oral. Thereafter, tacrolimus doses will be adjusted to maintain tacrolimus trough level of 5-7 ng/mL, and the patients will be maintained on low-dose tacrolimus monotherapy for duration of trial unless considered a treatment failure, and will be followed up for 3 years after transplantation surgery. For STANDARD Group, tacrolimus 0.15 mg/kg twice a day per oral with doses adjusted to whole blood trough level of 10-15 ng/mL for the first 6 months. Subsequently, doses will be adjusted to achieve trough tacrolimus level of 8-10 ng/mL. The first dose of tacrolimus must be administered within 12 hours after anastomosis.
Administration of oral Azathioprine in STANDARD group is once daily.
Administration of steroids in STANDARD group is either daily or alternate days. Total amount of steroid given to patients on Day 0 should not exceed methylprednisolone 1 gm or it equivalent. Minimum steroid dose for STANDARD group in maintenence phase is prednisolone 30 mg/week or its equivalent.
Patients in CAMPATH group will not receive Azathioprine or maintenance steroids. Total amount of steroid given to patients on Day 0 should not exceed methylprednisolone 1 gm or its equivalent.
Control group
Active

Outcomes
Primary outcome [1] 253393 0
Incidence of chronic lesions of Interstitial Fibrosis /Tubular Atrophy and calcineurin inhibitor nephrotoxicity on protocol biopsy
Timepoint [1] 253393 0
For both groups, followup will be from time of transplant surgery, unitl 36 months post transplant surgery.
Secondary outcome [1] 262477 0
All patients recruited into the study will be followed up for 3 years post transplant surgery or until patient death. Patient survival will be based on physical examination of patient at the institution.
Analyses will be by intention to treat.
Patient survival will be estimated by Kaplan-Meier method and comparison between the CAMPATH and STANDARD groups will be performed using the Log Rank test.
Timepoint [1] 262477 0
For both groups, followup will be from time of transplant surgery, and subsequently on Day 2, weekly from week 2 to 8, monthly from months 3 to 12 and at months 18, 24, 30 and 36.
Secondary outcome [2] 264063 0
All patients recruited into the study will be followed up for 3 years post transplant surgery or until patient death. Graft survival is defined by the presence of renal function adequate to prevent the patient from resuming maintenance dialysis.
Serum creatinine and urea, creatinine clearance and 24-hour urinary protein will also be measured at these time points.
Method: Blood and urine analysis
Timepoint [2] 264063 0
For both groups, followup will be from time of transplant surgery, and subsequently on Day 2, weekly from week 2 to 8, monthly from months 3 to 12 and at months 18, 24, 30 and 36.
Secondary outcome [3] 264064 0
Incidence of acute rejection (biopsy proven)
Timepoint [3] 264064 0
Acute rejection is defined by a >25% rise in serum creatinine from baseline, or other graft dysfunction that is confirmed by histological findings of rejection on allograft biopsy. For both groups, followup will be from time of transplant surgery, and subsequently on Day 2, weekly from week 2 to 8, monthly from months 3 to 12 and at months 18, 24, 30 and 36. Protocol biopsy will also be performed at 12 and 36 months after transplant.
Secondary outcome [4] 264065 0
Serum creatinine levels, method: blood analysis
Timepoint [4] 264065 0
For both groups, followup will be from time of transplant surgery, and subsequently on Day 2, weekly from week 2 to 8, monthly from months 3 to 12 and at months 18, 24, 30 and 36.
Secondary outcome [5] 264066 0
Creatinine clearance, calculated Nankivell and Modification of Diet in Renal Disease clearance
Timepoint [5] 264066 0
For both groups, creatinine clearance will be ,easured at Week 4 and months 3, 6, 12, 24 and 36 after transplant surgery. Nankivell and Medical of Diet In Renal Disease (MDRD) clearance will be determined at baseline, subsequently on Day 2, weekly from week 2 to 8, monthly from months 3 to 12 and at months 18, 24, 30 and 36.
Secondary outcome [6] 264067 0
Steroid resistant rejection, is defined as serum creatinine that continues to increase, or fails to return to within 25% of baseline within 1 week after treatment for rejection is started. A second episode of acute rejection occurring within 1 month after the index episode with apparent initial steroid responsiveness, is also defined as steroid resistant rejection.
Method: Blood analysis will be used to determine serum creatinine values.
Timepoint [6] 264067 0
For both groups, followup will be from time of transplant surgery, unitl 36 months post transplant surgery. Steroid resistant rejection occurring at any time point within the study period will be included in the analysis.
Secondary outcome [7] 264068 0
Incidence of chronic rejection. Chronic rejection will be diagnosed from histological examination of renal biopsy tissue; diagnosis and interpretation of renal biopsy will be based on Banff criteria.
Renal biopsy specimens will be obtained from protocol biopsies or may be obtained following biopsy for cause. Protocol renal biopsy will be performed for all patients at 12 and 36 month after transplant surgery. Biopsy for cause will be performed to evaluate renal dysfunction, proteinuria etc.
Timepoint [7] 264068 0
For both groups, followup will be from time of transplant surgery, until 36 months post transplant surgery. Chronic rejection occurring at any time point within the study period will be included in the analysis.
Secondary outcome [8] 264069 0
Delayed graft function is defined as the requirement for dialysis within the first week post transplantation without an intervening period of documented renal function. This will be determined by physical examination of the patient and analysing serum creatinine by blood analysis.
Timepoint [8] 264069 0
For both groups, followup will be from time of transplant surgery, unitl 36 months post transplant surgery.
Secondary outcome [9] 264070 0
Treatment failure from all causes is a composite end point that includes all causes of graft loss, all causes of patient death,steroid resistant rejection and grade II and above Interstitial Fibrosis And Tubular Atrophy (IF/TA) on post transplant biopsy.
Timepoint [9] 264070 0
For both groups, followup will be from time of transplant surgery, unitl 36 months post transplant surgery.
Secondary outcome [10] 264071 0
Actual steroid doses will be determined by determining patient's maintenance Prednisolone dose per day at designated time points. Cumulative steroid doses will be determined by the sum of all steroid doses given till the designated time point.
Timepoint [10] 264071 0
Steroid doses will be determined at 6, 12, 24 and 36 months after transplant surgery
Secondary outcome [11] 264072 0
Tacrolimus dose in mg/day and mg/kg/day
Timepoint [11] 264072 0
Tacrolimus doses will be determined at 6, 12, 24 and 36 months after transplant surgery
Secondary outcome [12] 264073 0
Lymphocyte counts will be measured by blood analysis.
Timepoint [12] 264073 0
Lymphocyte counts will be measured at baseline, Days 6, 7, weekly from week 2 to 8, monthly from months 3 to 12 and at months 18, 24, 30 and 36 after transplant surgery.
Secondary outcome [13] 264074 0
The UK Standard Short Form 36 Questionnaire (SF-36) will be used to assess Quality of Life. The questionnaire can be self administered or interviewer administered at the scheduled time of visit or assessment.
Timepoint [13] 264074 0
at first week, 6, 12, 24 and 36 months after transplantation

Eligibility
Key inclusion criteria
- Aged 18 – 65 years
- Renal failure with no previous renal transplantation
- Cadaveric or live donor kidney transplant recipient
- Written informed consent given
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant or nursing or woman of child bearing potential unwilling/unable to practice an acceptable form of birth control
- Major systemic or other illness that would, in the opinion of the investigator, interfere with the patient’s ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of study results
- Multi-organ transplant recipient
- Prior renal transplants
- Previous treatment with alemtuzumab
- Patient requiring anti-lymphocyte preparations/interleukin receptor antibody preparations for induction therapy
- Patient requiring cyclosporine, mycophenolic acid analogues or Mammalian Target of Rapamycin (mTOR) inhibitors as initial therapy
- Use of other investigational agents within 6 weeks prior to transplantation
- Active systemic infection
- Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen or anti-hepatitis C antibody positive (if Hepatitis C Virus Polymerase Chain Reaction (HCV PCR) unavailable) or Hepatitis C Virus Polymerase Chain Reaction (HCV PCR) positive
- Positive T lymphocyte cytotoxicity cross-match between recipient serum and donor cells
- Autoimmune hemolytic anemia
- Past history of anaphylaxis following exposure to humanised monoclonal antibodies
- Panel Reactive Antibodies (PRA) equal or greater than 50%
- Inability to undergo transplant biopsy, including patient who will require anticoagulation
- Cold ischemia time greater than 24 hours
- Patient whose graft function or perfusion cannot be demonstrated within 5 hours post-anastomosis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
- Direct Web based randomisation by Singapore Clinicl Research Institute
- Back up randomisation with envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
2: 1 randomisation in favor of Alemtuzumab
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/12/2009
Actual
8/02/2011
Date of last participant enrolment
Anticipated
Actual
9/02/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
63
Accrual to date
Final
Recruitment outside Australia
Country [1] 2346 0
Philippines
State/province [1] 2346 0
Country [2] 2347 0
Singapore
State/province [2] 2347 0

Funding & Sponsors
Funding source category [1] 256110 0
Government body
Name [1] 256110 0
National Medical Research Council
Country [1] 256110 0
Singapore
Funding source category [2] 256112 0
Government body
Name [2] 256112 0
Singhealth Pivotal Trials Grant
Country [2] 256112 0
Singapore
Primary sponsor type
Hospital
Name
National University Hospital
Address
5 Lower Kent Ridge Road
Singapore 119074
Country
Singapore
Secondary sponsor category [1] 251456 0
Hospital
Name [1] 251456 0
Singapore General Hospital
Address [1] 251456 0
Outram Road
Singapore 169608
Country [1] 251456 0
Singapore
Secondary sponsor category [2] 251457 0
Hospital
Name [2] 251457 0
National Kidney and Transplant Institute
Address [2] 251457 0
East Avenue
Quezon City 1100
Philippines
Country [2] 251457 0
Philippines

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258197 0
Domain Specific Review Board (DSRB)Domain E
Ethics committee address [1] 258197 0
National Healthcare Group (NHG) Head Quarter HQ, Clinical Project Management & Planning (CPMP) Division,
Research & Development Office (RDO)
No. 6, Commonwealth Lane,
GMTI Building, Level 4, Unit 01/02
Singapore 149547
Ethics committee country [1] 258197 0
Singapore
Date submitted for ethics approval [1] 258197 0
Approval date [1] 258197 0
26/06/2009
Ethics approval number [1] 258197 0
DSRB-E/09/077
Ethics committee name [2] 258200 0
Centralised Institutional Review Board (CIRB)
Ethics committee address [2] 258200 0
Singapore Health Services Private Limited
7 Hospital Drive, Block A, #03-01,
SingHealth Research Facilities,
169611
Ethics committee country [2] 258200 0
Singapore
Date submitted for ethics approval [2] 258200 0
Approval date [2] 258200 0
19/10/2009
Ethics approval number [2] 258200 0
2009/730/E
Ethics committee name [3] 258236 0
Institutional Review Board
Ethics committee address [3] 258236 0
Clinical Trial and Research Unit
National Kidney and Transplant Institute,
East Avenue,Quezon City,1100
Ethics committee country [3] 258236 0
Philippines
Date submitted for ethics approval [3] 258236 0
Approval date [3] 258236 0
12/09/2007
Ethics approval number [3] 258236 0
R-2007-009

Summary
Brief summary
The purpose of the study is to compare, following kidney transplantation, the safety and efficacy of alemtuzumab (MABCAMPATH) and low-dose tacrolimus (CAMPATH group) versus standard dose of tacrolimus with Azathioprine and Steroids (STANDARD group)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30564 0
Prof Anantharaman Vathsala
Address 30564 0
National University Hospital
NUHS Tower Block,
Level 10,
1E Kent Ridge Road,119228 Singapore.
Country 30564 0
Singapore
Phone 30564 0
+6567726124
Fax 30564 0
Email 30564 0
[email protected]
Contact person for public queries
Name 13811 0
Teoh Pui Li
Address 13811 0
National University Centre for Organ Transplant
National University Hospital
NUHS Tower Block,
Level 8,
1E Kent Ridge Road,119228 Singapore.
Country 13811 0
Singapore
Phone 13811 0
+6567726518
Fax 13811 0
+6567787913
Email 13811 0
[email protected]
Contact person for scientific queries
Name 4739 0
Teoh Pui Li
Address 4739 0
National University Centre for Organ Transplant
National University Hospital
NUHS Tower Block,
Level 8,
1E Kent Ridge Road,119228 Singapore.
Country 4739 0
Singapore
Phone 4739 0
+6567726518
Fax 4739 0
+6567787913
Email 4739 0
[email protected]

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Results publications and other study-related documents

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