1 vs 7 RATG Infusions in Renal Transplantation

Kidney Replacement Clinical Trial

— ONSET  

Official title:

Basiliximab With One Day or Seven Days RATG Induction Therapy in Renal Transplantation: a Matched-cohort Observational Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06374095
• Other study ID #: ONSET
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Mario Negri Institute for Pharmacological Research
• Contact: Piero L Ruggenenti, MD
• Phone: +3903545351
• Email: pruggenenti[@]asst-pg23.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This trial is to compare the risk/benefit profile over six-month follow-up of two induction immunosuppressive regimens based on one or seven low-dose perioperative RATG infusions on top of the same induction therapy with basiliximab and steroid (progressively tapered post-transplant) and maintenance therapy with calcineurin inhibitors and mycophenolate mofetil/mycophenolic acid in 75 recipients (25 Patients and 50 Reference-Patients) of a single or dual first kidney transplant from an ideal or marginal donor at a single Renal Transplant Center.

Description:

In patients receiving a kidney transplant, it is necessary to use immunosuppressive drugs that serve to reduce or prevent the risk of rejection. Some of these drugs are infused only in the first days of the transplant to more effectively reduce the reactivity of the immune system when the risk of rejection is highest. Among these are thymoglobulins, antibodies that destroy immune system cells (lymphocytes) which can cause rejection. For this reason, in their Center the investigators have developed a protocol that provides for the infusion of thymoglobulins for seven consecutive days starting from the day of the transplant. The first infusion begins even before the transplant is performed so that the lymphocytes are destroyed before the kidney is implanted and can therefore be recognized by the immune system as a foreign organ. This first administration is therefore certainly the most important, to the point that perhaps subsequent infusions of thymoglobulins may not even be necessary. Based on this reasoning, starting from April 1st 2023 the investigators began to infuse only the first dose of thymoglobulins, always starting the infusion before the transplant was performed, avoiding subsequent administrations. The goal was to maintain the same anti-rejection efficacy, but reducing the risk of side effects. In fact, thymoglobulins reduce the number of white blood cells and platelets in the blood and can increase the risk of opportunistic infections which are facilitated by the fact that the activity of the immune system is reduced by thymoglobulins. In other words, the effects of thymoglobulins on the immune system that serve to reduce the risk of rejection are the same as those that increase the risk of infections. At this point the investigators would therefore like to verify whether actually infusing a single dose of thymoglobulin starting before the transplant can maintain the same anti-rejection effect that is obtained by administering seven doses of thymoglobulin, while reducing the risk of side effects. For this reason, in this study they want to compare the data already collected for clinical reasons in kidney transplant recipients treated with a single dose of thymoglobulin with the data, also already collected, in kidney transplant recipients who instead received all seven doses of thymoglobulin. The latter must have the same characteristics as patients who have received a single dose of thymoglobulins. In essence the investigators should compare two groups of patients who are very similar in terms of the type of transplant performed (for example single or double) and the other anti-rejection therapies administered in addition to thymoglobulins and who differ only in having received one or seven infusions. All patients will have received the transplant from the same surgical team and will have been monitored and treated by the same nephrology team based on the same standardized clinical monitoring and immunosuppressive treatment protocols (regardless of the number of thymoglobulin doses). In this way, any differences in the risk of rejection or side effects that may emerge between the two groups could only be explained by the difference in treatment with thymoglobulins (with a single dose or with seven doses).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 75
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Consecutive recipients of a single or dual kidney transplant from ideal or marginal donors who, from 01/04/2023 to 31/12/2023, were induced with one single perioperative RATG infusion
• Consecutive recipients (Reference-Patients) of a single or dual kidney transplant from ideal or marginal donors who before 01/04/2023 were induced with seven perioperative RATG infusions (on top of the same induction and maintenance treatment used for patients receiving one single RATG infusion)

Exclusion Criteria:

• Living donor recipients, second transplant recipients or patients receiving a multiorgan transplant, and patients with a peak panel reactive antibody titer >30% or positive B cell cross-match

Related Conditions & MeSH terms

• Kidney Replacement

Intervention

Drug:
• RATG
Thymoglobulin, Genzyme corporation, Italy.
• Basiliximab
Simulect, Novartis, Italy.

Locations

Country	Name	City	State
Italy	ASST HPG23 - Unità di Nefrologia	Bergamo	BG

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Lebranchu Y, Bridoux F, Buchler M, Le Meur Y, Etienne I, Toupance O, Hurault de Ligny B, Touchard G, Moulin B, Le Pogamp P, Reigneau O, Guignard M, Rifle G. Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy. Am J Transplant. 2002 Jan;2(1):48-56. doi: 10.1034/j.1600-6143.2002.020109.x. — View Citation

Remuzzi G, Lesti M, Gotti E, Ganeva M, Dimitrov BD, Ene-Iordache B, Gherardi G, Donati D, Salvadori M, Sandrini S, Valente U, Segoloni G, Mourad G, Federico S, Rigotti P, Sparacino V, Bosmans JL, Perico N, Ruggenenti P. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet. 2004 Aug 7-13;364(9433):503-12. doi: 10.1016/S0140-6736(04)16808-6. — View Citation

Thiyagarajan UM, Ponnuswamy A, Bagul A. Thymoglobulin and its use in renal transplantation: a review. Am J Nephrol. 2013;37(6):586-601. doi: 10.1159/000351643. Epub 2013 Jun 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of thrombocytopenia and/or leukopenia	Incidence of thrombocytopenia and/or leukopenia requiring or not requiring down-titration or transient withdrawal of mycophenolate mofetil/ mycophenolic acid (and/or RATG)	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of anemia	Occurrence of anemia requiring treatment with erythropoiesis stimulating agents	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of viral infections	Polyomavirus BK (BKV) and/or Cytomegalovirus (CMV) infection/reactivations	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of pneumonia	Pneumocystis carinii pneumonia	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of opportunistic infections	Systemic candidiasis and any other opportunistic infection	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of delayed graft function	Delayed Graft Function defined as need of dialysis during the first week post-transplant	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of allograft rejection	Acute allograft rejection (overall, steroid-resistant and biopsy-proven rejections considered separately)	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Occurrence of biopsy proven rejection	Banff score for biopsy proven rejections	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Survival	Six-month patient/graft survival	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Platelet and WBC counts	Six-month time course of platelet and WBC counts	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Creatinine levels	Six-month time course of serum creatinine levels	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months
Secondary	Adverse events	Incidence of serious and non-serious adverse events	From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months