Condition category
Urological and Genital Diseases
Date applied
28/02/2006
Date assigned
23/03/2006
Last edited
25/09/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Richard Baker

ORCID ID

Contact details

Renal Unit
Linclon Wing
St James's Hospital
Becket Street
Leeds
LS9 7TF
United Kingdom

Additional identifiers

EudraCT number

2006-000830-11

ClinicalTrials.gov number

Protocol/serial number

RL05/7239

Study information

Scientific title

Acronym

SALAMI

Study hypothesis

To compare the efficacy of two tacrolimus based steroid avoidance regimes. This is an equivalence study with no anticipated difference in major endpoints between the two arms.

Ethics approval

Ethics approval received from the Leeds (East) Research Ethics Committee on the 26th July 2006 (ref: 06/Q1206/64, EudraCT No: 2006-000830-11).

Study design

Phase IV, open label, single centre, randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Renal transplant immunosuppression

Intervention

Comparing two immunosuppression regimes:
1. Control (standard regime) - intra-operative Basiliximab and steroids followed by maintenance with Tacrolimus and MMF
2. Steroids intra-operative followed by Alemtuzumab then maintenence with Tacrolimus

Intervention type

Drug

Phase

Phase IV

Drug names

Basiliximab, Tacrolimus, MMF, Alemtuzumab

Primary outcome measures

Diethylene triamine pentaacetate (DTPA) isotopic glomerular filtration rate (GFR) at 12 months

Secondary outcome measures

1. Patient and graft survival
2. Incidence and duration of delayed graft function
3. Incidence and severity of steroid-treated presumptive and biopsy-confirmed acute rejection
4. Comparison of blood pressure control between groups by clinic readings, number of agents used and 24 hour monitoring at 6 and 12 months
5. Comparison of groups by pulse wave analysis, a powerful surrogate marker for cardiovascular outcome, at baseline, 6 and 12 months
6. Incidence of impaired glucose tolerance, weight gain and diabetes at 6 weeks, 6 and 12 months
7. Assessment of quality of life by questionnaires at 6 and 12 months
8. Assessment of adherence, looking at trough tacrolimus level variations between two groups
9. Economic analysis of the cost-effectiveness of both regimes
10. Comprehensive assessment of clinically indicated, implantation and one year protocol biopsies by:
10.1. Morphological scoring by Banff/chronic allograft damage index (CADI) system
10.2. Assessment of fibrosis by specific stains
10.3. Genomic analysis for products associated with ischaemia reperfusion, immune activation, inflammation and fibrosis
11. Analysis of urine and blood by proteomics at baseline, 3 months, 6 months, 12 months and other clinically indicated time points
12. Analysis of T cells for development of regulatory T cells
13. Analysis of anti-donor antibody responses
14. Monitoring of B and T cell subsets by flow cytometry
15. Monitoring of infectious complications/pathogens - including cytomegalovirus (CMV) infection and infections with polyomaviruses
16. Incidence of post transplant malignancies including post-transplant lymphoproliferative disease (PTLD)
17. Biochemical and haematological monitoring

Overall trial start date

01/04/2006

Overall trial end date

01/05/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male and female patients who must be over age 18 years
2. Patients must be recipients of heart-beating cadaveric, non-heart beating or living donors
3. Patients receiving a 2nd or subsequent grafts must have maintained their primary graft for a minimum of 6 months, except if graft failure was due to technical reasons
4. Written informed consent
5. Women at risk of pregnancy must have a negative pregnancy test before commencing the trial and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuing the trial. The manufacturer of Alemtuzumab advises effective contraception for 6 months after administration to men or women. Advice will be given to patients to discuss with the transplant medical staff if a pregnancy is planned.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120

Participant exclusion criteria

1. Regional patients from Hull Royal Infirmary (due to the logistical difficulties in following these patients up from Leeds)
2. High Risk Recipients - defined as recipients who have one or more of the following: 2 human leukocyte antigen, type DR (HLA-DR) mismatch, previous immunologically mediated graft loss in less than 6 months, preoperative donor specific antibodies
3. Known hypersensitivity to the investigational medicinal product (IMP) including the standard drugs
4. Prohibited prior or concomitant medications
5. Pregnant women or nursing mothers
6. White blood cell count (WBC) count <3000/mm^3 or platelets <75,000/mm^3 at time of study entry
7. Any other concurrent cardiovascular, gastrointestinal, pulmonary or haematological conditions that would restrict the administration of study drugs in the opinion of the investigator

Recruitment start date

01/04/2006

Recruitment end date

01/05/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Renal Unit
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

Leeds Teaching Hospitals NHS Trust (UK)

Sponsor details

Research and Development Dept.
6th Floor Wellcome Wing
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom

Sponsor type

Government

Website

http://www.leedsth.nhs.uk/sites/research_and_development/

Funders

Funder type

Government

Funder name

Leeds Teaching Hospitals NHS Trust (UK) - research fund

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22390816
2. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24056618

Publication citations

  1. Results

    Cherukuri A, Salama AD, Carter C, Smalle N, McCurtin R, Hewitt EW, Hernandez-Fuentes M, Clark B, Baker RJ, An analysis of lymphocyte phenotype after steroid avoidance with either alemtuzumab or basiliximab induction in renal transplantation., Am. J. Transplant., 2012, 12, 4, 919-931, doi: 10.1111/j.1600-6143.2011.03891.x.

  2. Results

    Welberry Smith MP, Cherukuri A, Newstead CG, Lewington AJ, Ahmad N, Menon K, Pollard SG, Prasad P, Tibble S, Giddings E, Baker RJ, Alemtuzumab induction in renal transplantation permits safe steroid avoidance with tacrolimus monotherapy: a randomized controlled trial., Transplantation, 2013, 96, 12, 1082-1088, doi: 10.1097/TP.0b013e3182a64db9.

Additional files

Editorial Notes