cardiovascular risk during prophylaxis of graft rejection in renal transplant recipients cardiovascular risk while preventing rejection of kidney transplant
Conditions
Interventions
Belatacept arm:
Belatacept will be dosed 5 mg/kg IV on day 1, 15, 29, 43, 57 and then every
month thereafter. CNI to be tapered as follows: 100% on day 1, to 70-80% on day
7, to 40-60% on day 15, 20
tacrolimus
concentrations will be kept at 5-10 ng/ml. Target concentrations may be
modified according to local directives, and vary with time since
transplantation.
Belatacept
Cardiovascular risk
renal transplant recipients
Sponsors
University Hospital Uppsala
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Signed Written Informed Consent 2. Target Population: 2.a Renal transplant recipients of living donor or deceased donor kidney transplant. 2.b Stable renal graft (eGFR > 20 ml/min) with no need for exploratory examination) 2.c Tacrolimus or CsA (Cyclosporine A) standard treatment since transplantation 2.d 3 * 60 months post-transplantation at randomization 3. Age and Sex: 3.a Men and women, aged 18 to 80 years, both inclusive 3.b Women of childbearing potential (WOCBP) must be using adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug to minimize the risk of pregnancy. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post- menopausal. Post-menopause is defined as: *Amenorrhea that has lasted for 12 consecutive months without another cause, or *For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where their partner is sterile (e.g. vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product (belatacept).
Exclusion criteria
Exclusion criteria: 1. Sex and Reproductive Status: 1.a Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug. 1.b Women who are pregnant or breastfeeding. 1.c Women with a positive pregnancy test. 2. Target Disease Exceptions: Subjects who are Epstein-Barr virus IgG negative or have unknown IgG status for EBV. 3. Medical History and Concurrent Diseases: 3.a De novo or recurrent underlying renal disease that, in the investigator's opinion, could adversely influence the current allograft 3.b History of vascular or antibody-mediated rejection in the present transplant 3.c Ongoing serious infections, as per investigator's opinion 3.d Signs of post-transplant lymphoproliferative disorder 3.e History of tuberculosis. If the patient has a history of active TB or a history of latent untreated TB, the patient must be excluded from the study. If the patient has a history of latent treated TB, the patient can be included. 3.f Signs of malignancy. Exceptions are BCC/SCC or non-malignant melanoma 3.g History of malignancy, unless subject has been considered to have fully recovered from malignancy since >1 year, without any signs of relapse 3.h Life expectancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary end-point is the estimated risk of major adverse cardiovascular events (MACE). The natural logarithm of the estimated CV risk for MACE will be calculated as previously described by Soveri et al. (2012) as a linear function of the following variables: age, previous coronary heart disease, smoking, serum creatinine, diabetes mellitus, LDL-cholesterol and number of transplants. The primary endpoint will be a comparison of the log of the estimated CV risk between treatment groups (CNI vs. belatacept based immunosuppression) at one year. For patients discontinuing the study before one year, the last available estimate of CV risk will be used in the analysis of the ITT population. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary end-points are the comparisons between treatments arms for: - individual components of CV risk in RTR: blood pressure, lipid profiles and eGFR. - vascular function measured by EndoPAT. - biomarkers of ageing (bio-ageing) in RTR: leukocyte telomere length, CDKN2A levels, leukocyte RNA expression profile. - biomarkers for CV risk factors in RTR measured by Proximity Ligation Assay, ELISA, multicoloured FACS analyses (Dutch sites only), SDF Imaging (Dutch sites only) and miRNA measurements - renal transplant biopsy IFTA scores (Banff criteria) - expression of graft fibrosis markers, and other measures of chronic renal transplant markers in kidney biopsies - acute rejection - allograft losses - CV events occurring during the study, i.e. o cardiovascular death (due to myocardial infarction (MCI), heart failure or stroke), o non fatal MCI o non fatal stroke o hospitalization due to congestive heart failure o hospitalization due to angina pectoris o coronary intervention - patient survival - safety and tolerability | — |
Countries
The Netherlands
Outcome results
None listed