Optimized TacrolimuS and MMF for HLA Antibodies after Renal Transplantation

• Register: ISRCTN
• Last refreshed on: 6 February 2023
• Main ID: ISRCTN46157828
• Date of registration: 26/03/2013
• Prospective Registration: Yes
• Primary sponsor: King's College London (UK)
• Public title: Optimized TacrolimuS and MMF for HLA Antibodies after Renal Transplantation
• Scientific title: A randomized controlled clinical trial to determine if a combined screening /treatment programme can prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies
• Date of first enrolment: 01/09/2013
• Target sample size: 3000
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN46157828
• Study type: Interventional
• Study design: Randomised; Interventional; Design type: Screening, Treatment (Treatment)
• Phase: Not Applicable

Countries of recruitment

England, United Kingdom

Contacts

• Name: Anthony Dorling

Key inclusion & exclusion criteria

Inclusion criteria:
1. Renal transplant recipients >1 year post transplantation
2. Aged 18-70 years, male and female
3. Estimated glomerular filtration rate (eGFR) of >=30

Exclusion criteria:
1. Recipient requiring HLA desensitisation to remove antibody for a positive XM transplant
2. Recipient known already to have HLA antibody who has received specific intervention for that antibody or for CAMR / chronic rejection
3. Recipient of additional solid organ transplants (e.g. pancreas, heart, etc).
4. History of malignancy in previous 5 years (excluding non-melanomatous tumours limited to skin)
5. HBsAg+,HBcAb+, HepC+ or HIV+ recipient (on test performed within previous 5 years)
6. History of acute rejection requiring escalation of immunosuppression in the 6 months prior to screening.
7. History of an ongoing or previous infection (no time limit) that would prevent optimization of immunosuppression, including ocular Herpes simplex.
8. Known hypersensitivity to any of the IMPs
9. Known hereditary disorders of carbohydrate metabolism
10. Patient enrolled in any other studies involving administration of another IMP at time of recruitment
11. Pregnancy or breastfeeding females (based on verbal history of recipient)
12. Pre-menopausal females who refuse to consent to using suitable methods of contraception throughout the trial.


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Topic: Renal and Urogenital; Subtopic: Renal and Urogenital (all Subtopics); Disease: Renal
Injury, Occupational Diseases, Poisoning
Kidney transplant failure and rejection

Intervention(s)

Optimized Treatment protocol, The 'optimized treatment' protocol in the recruits with HLA Ab in unblinded group will be:
1. Mycophenolate mofetil bd, tds or qds, or enteric coated mycophenolic acid bd, with daily dose determined according to local unit guidelines. The patient will be stabilized on the maximum tolerated dose.
2. Tacrolimus od or bd, according to local unit preference, with dose titrated to achieve 12-hour post-dose levels of 4g/L to 8g/L (4-8 ng/ml). The patient will be stabilized on the maximumtolerated dose that achieves these levels.
3. Prednisolone od. Starting at 20mg for two weeks, then reducing by 5 mg od every two weeks down to a maintenance dose of 5mg od.
Screening for HLA antibodies, Serum prepared from 10mls of blood will be used in the commercially available 'LABScreen' tests, containing fluorescently tagged beads coated with purified HLA antigens. All participating centres have 'Luminex' equipment for analysis of these tests and the skills to process samples and interpret results. Therefore, the tests will be performed in each of the centres.

Follow-Up Length: 36 month(s)

Primary Outcome(s)

Current primary outcome measure as of 12/05/2020:
Determine the time to graft failure in patients testing positive for HLA Ab at baseline or within 32 months of randomization who receive an optimized anti-rejection medication intervention with prednisone, Tac and MMF (‘treatment’), compared to a control group who test positive for HLA Ab at baseline or within 32 months post-randomization who remain on their established immunotherapy and whose clinicians are not aware of their Ab status. The primary endpoint will be assessed remotely when a minimum of 43 months post-randomisation has been achieved by all.

Previous primary outcome measure:
Renal Transplant Failure Rates; Timepoint(s): 3 Years post-recruitment

Secondary Outcome(s)

Current secondary outcome measures as of 12/05/2020:
1. Analysis of adherence and perceptions of risk; Timepoint(s): 32 months
2. Change in estimated Glomerular Filtration Rate; Timepoint(s): 32 months
3. Patient Survival; Timepoint(s): 32 months
4. Proteinuria; Timepoint(s): 32 months
5. Rate of acute rejection; Timepoint(s): 32 months
6. Rates of biopsy proven malignancy; Timepoint(s): 32 months
7. Rates of Culture-positive infection; Timepoint(s): 32 months
8. Rates of Diabetes Mellitus; Timepoint(s): 32 months
9. Scientific analyses of humoral & cellular immunity and CD34+ cells; Timepoint(s): 32 months


Previous secondary outcome measures:
1. Analysis of adherence and perceptions of risk; Timepoint(s): 3 years
2. Change in estimated Glomerular Filtration Rate; Timepoint(s): 3 years
3. Patient Survival; Timepoint(s): 3 years
4. Proteinuria; Timepoint(s): 3 years
5. Rate of acute rejection; Timepoint(s): 3 years
6. Rates of biopsy proven malignancy; Timepoint(s): 3 years
7. Rates of Culture-positive infection; Timepoint(s): 3 years
8. Rates of Diabetes Mellitus; Timepoint(s): 3 years
9. Scientific analyses of humoral & cellular immunity and CD34+ cells; Timepoint(s): 3 year

Secondary ID(s)

2012-004308-36

13990

Source(s) of Monetary Support

NIHR (UK) - Efficacy and Mechanism Evaluation; Grant Codes: 11/100/34

Ethics review

Status:
Approval date:
Contact:

NRES Committee London - Hampstead, 14/01/2013, ref: 12/LO/1759

Results

• Results available: Yes
• Date Completed: 30/09/2020