Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients (TRAINING)
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|ClinicalTrials.gov Identifier: NCT04936282|
Recruitment Status : Not yet recruiting
First Posted : June 23, 2021
Last Update Posted : June 23, 2021
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Background: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α klotho levels, progression of IFTA, and loss of kidney function.
Methods: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-TX, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant Failure and Rejection||Drug: Grafalon Drug: Normal Treatment: Steroids, tacrolimus and mycophenolate||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study|
|Estimated Study Start Date :||January 2022|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||December 2024|
Experimental: Steroids, tacrolimus, mycophenolate and Grafalon
Normal treatment for first 90 days, then add Grafalon single-dose if borderline lesions are present in protocol biopsy (performed at third month post-transplantation)
When Borderline lesions are present in protocol biopsy, administer Grafalon ® 6 mg/kg/day in a single day.
Active Comparator: Steroids, tacrolimus and mycophenolate
Normal treatment arm
Drug: Normal Treatment: Steroids, tacrolimus and mycophenolate
When Borderline lesions are present in protocol biopsy, administer treatment according to routine clinical practice
- Presence of interstitial fibrosis/tubular atrophy (IFTA) [ Time Frame: 24 months ]Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant.
- Renal function [ Time Frame: 24 months ]Renal function after kidney transplant in both groups at 24 months measured according to glomerular filtration rate determined by CKD-EPI formula
- Graft Survival [ Time Frame: 24 months ]Graft survival after kidney transplant in both groups
- Patient Survival [ Time Frame: 24 months ]Patient survival after kidney transplant in both groups
- Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups [ Time Frame: 24 months ]The Basle scale was used to assess adherence (BAASIS questionnaire) to immunosuppressive therapy.
- Incidence of Diabetes Mellitus [ Time Frame: 24 months ]Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months
- Blood Pressure [ Time Frame: 24 months ]Blood pressure after kidney transplant in both groups at 24 months
- Number of Participants With Acute Rejection Lesions [ Time Frame: 24 months ]Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification
- Lipid Profile [ Time Frame: 24 months ]Lipid profile after kidney transplant in both groups at 24 months
- Klotho levels [ Time Frame: 24 months ]Klotho levels after kidney transplant in both groups at 1, 3, 6, 12 and 24 months
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients of either sex, older than 18 years, with no immunological risk (PRA<20% and absence of DSA), who receive their first deceased donor or living donor KT.
- Presence of BL, excluding isolated inflammation (t0, i>0) and isolated tubulitis (t>0, i0).
- Patients receiving tacrolimus in combination with mycophenolic acid (MPA) and steroids.
- Absence of clinical or subclinical and histological immunological dysfunction before randomization.
- Absence of de novo DSA anti-HLA antibodies at the time of randomization.
- Provision of written informed consent.
- Acceptance of efficient contraception in women.
- Recipients of a multi-organ transplant.
- Patients without inflammation in the third month protocol biopsy (i0,t0), or with isolated inflammation without tubulitis (t0,i>0) or isolated tubulitis without inflammation (t>0,i0).
- Presence of DSA antibodies before transplantation or at randomization.
- Cold ischemia time >30 hours.
- Serum creatinine >2 mg/dl or proteinuria >1 g/day at randomization.
- Presence of significant thrombopenia (<100,000/mm3) or leukopenia (<3000 mm/3) at randomization.
- Previous episode of clinical or subclinical rejection (≥IA) before randomization.
- Presence of BL before randomization.
- CMV infection or disease in the first three months after transplantation.
- BK-polyomavirus nephropathy at randomization.
- Recurrent or de novo glomerulonephritis.
- Treatment with immunosuppressive drugs other than those in this clinical trial.
- Patients who are positive for the human immunodeficiency virus (HIV) or with severe systemic infection, who, in the opinion of the investigator, require continued therapy.
- Previous (within the last 5 years) or present malignancy, except excised basal or squamous cell carcinoma.
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): NCT04936282
|Contact: Pedro Ruiz-Esteban, PhDemail@example.com|
|Hospital Universitario de Canarias|
|Tenerife, None Selected, Spain, 38320|
|Contact: Armando Torres, MD,PhD firstname.lastname@example.org|
|Barcelona, Spain, 08025|
|Contact: Luis Guirado, MD, PhD|
|Hospital Universitari Valld´Hebron|
|Barcelona, Spain, 08035|
|Contact: Manel Perello, MD|
|Hospital Regional Universitario de Málaga|
|Malaga, Spain, 29010|
|Contact: Domingo Hernández, MD, PhD|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Fundación Canaria de Investigación Sanitaria|
|Other Study ID Numbers:||
|First Posted:||June 23, 2021 Key Record Dates|
|Last Update Posted:||June 23, 2021|
|Last Verified:||June 2021|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
low immunological risk
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action