Tacrolimus After rATG and Infliximab Induction Immunosuppression (RIMINI) (RIMINI)
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|ClinicalTrials.gov Identifier: NCT04114188|
Recruitment Status : Recruiting
First Posted : October 3, 2019
Last Update Posted : October 9, 2019
|Condition or disease||Intervention/treatment||Phase|
|Renal Transplant Rejection||Drug: Antithymocyte Immunoglobulin (Rabbit)||Phase 2|
A total of 75 patients will receive the proposed induction regimen, with expected 68 completers accounting for drop-outs and non-compliances with the protocol. If up to 27 out of the 68 completers experience efficacy failure, a progression into a larger trial will be considered justifiable. If the number of patients experiencing efficacy failure is between 28 and 34 out of 68, the merits of a larger non-inferiority design will be considered depending on the risk/benefit assessment. If more than 34 out of the 68 completers experience efficacy failure, a progression into a larger trial would be considered unjustifiable. 1st kidney transplant recipients (low risk: PRA/cPRA < 20%, no DSA) will receive short rATG induction (2x1.5 mg/kg) given perioperatively and on first postoperative day. All patients will receive one shot Infliximab mAb at day 2. Since POD1, maintenance IS consists of Tac and tapered steroids therapy. All patients will be followed up for one year.
At the POD 0 the first rATG dose (1.5mg/kg) will be given according to the local practice and Methyprednisolon 500mg will be given before reperfusion. At the POD 1 patients will receive methylprednisolon 500mg i.v. followed by second rATG dose (1.5mg/kg). Infliximab 5mg/kg b.w. will be given in slow infusion on POD2. Tacrolimus will be given the first dose before surgery at dose 0.1 mg/kg and next from POD1 at 0.2mg/kg/day and doses adjusted according to blood trough levels (10-15 ng/mL, POD1-POD13, 5-8ng/mL POD 14-90, 4-6ng/mL POD >90. Prednison (or appropriate dose of methylprednisolone) will be initiated POD 2 at a dose of 20mg/day and slowly tapered down to 5 mg at the POD 7 (POD2: 20mg, POD3: 15mg, POD4-5: 10mg, POD6-7: 7,5mg, > POD7: 5mg).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a confidence-interval-estimation based early phase design, aiming to estimate a plausible range of the population treatment effect which is not bound to a formal hypothesis.|
|Masking:||None (Open Label)|
|Official Title:||Tacrolimus After rATG and Infliximab Induction Immunosuppression (RIMINI)|
|Actual Study Start Date :||December 2016|
|Estimated Primary Completion Date :||October 2019|
|Estimated Study Completion Date :||December 2020|
Experimental: Antithymocyte Immunoglobulin (Rabbit)
rATG induction on day 0 & 1 post op
Drug: Antithymocyte Immunoglobulin (Rabbit)
1st kidney transplant recipients (low risk: PRA/cPRA < 20%, no DSA) will receive short rATG induction (2x1.5 mg/kg) given perioperatively and on first postoperative day. All patients will receive one shot Infliximab mAb at day 2. Since POD1, maintenance IS consists of Tac and tapered steroids therapy.
- Composite endpoint of efficacy failure [(treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up) and renal function (estimated glomerular filtration rate)] of the induction regimen [ Time Frame: 12 months post transplantation ]Composite endpoint of efficacy failure of the induction regimen defined as occurrence of any of the following individual outcomes up to 12 months post transplantation (start of follow up at transplantation): acute rejection, graft loss or poor graft function defined as eGFR<40 ml/min.
- Prevalence of biomarker signatures at 6, 12 months of follow-up. [ Time Frame: 6, 12 months of follow-up ]
The following biomarker analyses are implemented in the trial:
- EBV/CMV/BKV load + CMV/EBV T-Ly
- Multi-parameter flow cytometry
- gene expression profiling
- urinary IP-10
- HO-1 polymorphisms
- histology (protocol/induced biopsies)
- Incidence of death by 12 months post-transplantation [ Time Frame: 12 months post-transplantation ]incidence of death by 12 month post transplantation
- Incidence of graft loss by 12 months post-transplantation [ Time Frame: 12 months post-transplantation ]Incidence of graft loss by 12 months post-transplantation
- Incidence of metabolic and cardiovascular co-morbidity by 12 months post-transplantation [ Time Frame: 12 months post-transplantation ]Incidence of metabolic and cardiovascular co-morbidity by 12 months post-transplantation (post-transplant diabetes mellitus, dyslipidemia, hypertension, myocardial infarction, stroke, peripheral vascular disease)
- Proportion of subjects who remain on tacrolimus/steroids therapy at 12 months post-transplantation [ Time Frame: 12 months post-transplantation ]Proportion of subjects who remain on tacrolimus/steroids therapy at 12 months post-transplantation
- Incidence of acute and chronic lesions assessed by the Banff 07 score in protocol biopsy at 12months post-transplantation [ Time Frame: 12 months post-transplantation ]
- Antibody mediated rejection
- T cell mediated rejection:
Type IA: cases with significant interstitial infiltration (> 25% of parenchyma affected, i2 or i3) & foci of moderate tubulitis (t2) Type IB: cases with significant interstitial infiltration (> 25% of parenchyma affected, i2 or i3) & foci of severe tubulitis (t3) Type IIA: cases with mild to moderate intimal arteritis (v1) Type IIB: cases with severe intimal arteritis comprising > 25% of luminal area (v2) Type III: cases with transmural arteritis or arterial fibrinoid change & necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3) Chronic allograft arteriopathy
- Interstitial fibrosis and tubular atrophy: Grade I: mild interstitial fibrosis & tubular atrophy Grade II: moderate interstitial fibrosis & tubular atrophy Grade III: severe interstitial fibrosis & tubular atrophy/loss
- Incidence of discontinuation of study treatment [ Time Frame: 12 month ]Incidence of discontinuation of study treatment
- Donor specific antibody (DSA) at 12M [ Time Frame: 12 months post-transplantation ]Assessment of donor specific antibody at 12M Method of assessment: Luminex assay
- Overall safety of tacrolimus/steroids therapy immunosuppressive regimen measured by the occurrence of viral and bacterial infections, malignancies and autoimmunity. [ Time Frame: 12 month ]Overall safety of tacrolimus/steroids therapy immunosuppressive regimen measured by the occurrence of viral and bacterial infections, malignancies and autoimmunity
- Health-related quality of life using SF-36v2 questionnaires at baseline (pre Transplantation), Month 1, Month 3, Month 6, and Month 12 [ Time Frame: baseline (pre transplantation), Month 1, Month 3, Month 6, and Month12 ]
The SF-36v2 provides scores for each of the eight health domains and psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health
- Assessment of patient-specific resource consumption using a trial specific questionnaire at initial discharge, Month 3, Month 6, Month 12, and in cases of repeated hospitalization [ Time Frame: initial discharge, Month 3, Month 6, Month 12, and in cases of repeated hospitalization ]
The questionnaires capture relevant apsects of resource consumption:
- In which ward(s) a patient was hospitalized
- Additional services (diagnostics / procedures / operations)
- Potential dialysis procedures (past and expected frequency in the future)
- Potential outpatient visits and the services consumed
- Employment status and potential depency on care-giving The completion requires a review of inpatient records. Part II and Part III also require a short interview with the patient about potential outpatient visits during the study period, their employment status, and potential depedency on care-giving.
- Health-related quality of life using EQ5D-5L questionnaires at baseline (pre Transplantation), Month 1, Month 3, Month 6, and Month 12 [ Time Frame: baseline (pre transplantation), Month 1, Month 3, Month 6, and Month12 ]
EQ-5D is a standardized instrument for measuring generic health status. It has been widely used in population health surveys, clinical studies, economic evaluation and in routine outcome measurement in the delivery of operational healthcare.
The EQ-5D-5L is a Patient Reported Outcome (PRO) instrument that can generally assess the quality of life of patients, regardless of their disease, over 6 questions. It also includes a vertical EQ visual analog scale (EQ VAS, 0-100 points) and a descriptive EQ-5D-5L system, which considers the following 5 dimensions or subscales over 5 levels or possible answers.
dimensions: mobility, self-sufficiency, General Activities, Pain / Physical complaints, fear / dejectedness levels: Level 1: No problems/ No pain/ Not afraid; Level 2: Slight problems/ Slight pain/ A little anxious; Level 3: Moderate problems/ Moderate pain/ Moderate anxiety; Level 4: Major problems / Severe pain/ Very anxious; Level 5: Not able to/ Extreme pain/ Extremely anxious
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04114188
|Contact: Petra Reinke, PhD, MDfirstname.lastname@example.org|
|Contact: Ondrej Viklicky, PhD, MDemail@example.com|
|Charité University Medicine Berlin||Recruiting|
|Berlin, Germany, 13353|
|Contact: Petra Reinke, PhD, MD firstname.lastname@example.org|
|Principal Investigator: Ondrej Viklicky, PhD, MD|
|Study Chair:||Reinke Reinke, PhD, MD||Charité University medicine Berlin, Germany|
|Principal Investigator:||Ondrej Viklicky, PhD, MD||Institute for Clinical and Experimental Medicine|