Comparison of the Efficacy and Safety of Sirolimus Versus Everolimus Versus Mycophenolate in Kidney Transplantation (SEM)

Comparison of the Efficacy and Safety of Sirolimus, Everolimus or Mycophenolate in Renal Transplant Recipients Receiving Induction With Anti-thymocyte Globulin, Tacrolimus and Prednisone

This study was designed to compare 3 immunosuppression regimens: sirolimus and tacrolimus versus everolimus and tacrolimus versus mycophenolate and tacrolimus.

The primary outcome is the incidence of cytomegalovirus infection / disease, a relevant medical need in the absence of pharmacological prophylaxis.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Infection
• Intervention / Treatment: Drug: Sirolimus; Drug: Everolimus; Drug: Mycophenolic acid

• Study Type: Interventional
• Enrollment (Actual): 1209
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 04038002
      • Hospital do Rim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Recipients, adults of the first living or deceased donor kidney transplant;
2. Patients who agreed to participate in the study and signed the informed consent form

Exclusion Criteria:

1. Receptors with a medical history of nephrotic syndrome or focal and segmental glomerulosclerosis confirmed as the etiology of end-stage renal disease;
2. Receptors with poor understanding about chronic kidney disease and its treatment alternatives;
3. Receptors with early history of non compliance to treatment with immunosuppressive drugs;
4. Retransplantation;
5. Multi-organ recipients;
6. Recipients with BMI> 30 kg / m2;
7. KDPI> 80%;
8. Cold ischemia time greater than 24 hours;
9. Receptors with a percentage of anti-HLA antibodies above 50%, either class I or Class II;
10. Women of childbearing potential who do not undertake contraceptive methods (condoms or oral contraceptives).
11. Patients receiving immunosuppressive therapy prior to transplantation, except low dose of prednisone;
12. Patients with severe uncontrolled dyslipidemia;
13. Patients who have a known contraindication for administration of any of the immunosuppressive drugs provided for in this study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sirolimus +tacrolimus; Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL.	Drug: Sirolimus; sirolimus combined to reduced dose of tacrolimus; Other Names: Rapamune
Experimental: everolimus +tacrolimus; Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL.	Drug: Everolimus; everolimus combined to reduced dose of tacrolimus; Other Names: Certican
Active Comparator: mycophenolate +tacrolimus; Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID).	Drug: Mycophenolic acid; Control arm: mycophenolate combined to regular tacrolimus; Other Names: mycophenolate sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Cytomegalovirus Infection or Disease	Incidence of CMV infection/disease in three study groups (SRL, EVR anda MPS).	12 months follow up

Collaborators and Investigators

• Sponsor: Hospital do Rim e Hipertensão

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2017
• Primary Completion (Actual): March 18, 2021
• Study Completion (Actual): August 23, 2021

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Everolimus; Sirolimus
• Other Study ID Numbers: HRHipertensao

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes