Estudio aleatorizado y abierto, comparativo de la seguridad y la eficacia del cambio de un inhibidor de la calcineurina a sirolimus frente a la continuación del uso de un inhibidor de la calcineurina en trasplantados cardiacos con insuficiencia renal de grado leve a moderado A Randomized, Open-Label Study to Compare the Safety and Efficacy of ConversionFrom a Calcineurin Inhibitor to Sirolimus Versus Continued Use of a CalcineurinInhibitor in Cardiac Transplant Recipients With Mild to Moderate Renal Insufficiency

Phase 1

Active, not recruiting

• Conditions: Trasplantados cardiacos con insuficiencia renal de grado leve a moderado Cardiac transplant recipients with mild to moderate renal insufficiency.

• Registration Number: EUCTR2006-002420-41-ES
• Lead Sponsor: Wyeth Research, Division of Wyeth Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-10
• Study Completion: 2010-05-21
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1.Cardiac transplant recipients aged greater than/equal to 18 years.
2.Receiving CsA or TAC as part of the maintenance immunosuppressive regimen since the time of transplantation.
3.12 Months after cardiac transplantation but equal to or less than 96 months after transplantation at the time of screening.
4.GFR > 40 mL/min but < 90 mL/min/1,73m2 (calculated by the Cockcroft-Gault equation and adjusted for bosy surface area [BSA] using the Mosteller formula) with stable renal function (as defined by no decrease > 20% of GFR) over the previous 3 months.
5.Left ventricular ejection fraction by echocardiogram (ECHO) greater than/equal to 40%.
6.Women of childbearing potential (CBP) must have a negative urine pregnancy test before randomization.
7.Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the treatment period.
8.Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception for 3 months after discontinuation of assigned treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Secondary cardiac transplant recipients (subjects who have lost 1 or more previous cardiac transplant).
2.Multiple-organ transplant recipients (such as heart-lung, heart-kidney, or heart-after-kidney transplant recipients).
3.Treatment of acute rejection within 3 months.
4.Evidence of active systemic or localized major infection at the time of randomization.
5.Evidence of infiltrate, cavitation or consolidation on chest x-ray film obtained within 3 months before or at the time of the screening evaluation.
6.Use of any investigational drug or treatment up to 4 weeks before random assignment.
7.Spot urine protein-to-creatinine ratio > 0.5 or proteinuria > 500 mg/day.
8.Subjects maintained on CNI monotherapy.
9.Prior or current use of mammalian target of rapamycin (mTOR) inhibitors unless administration was part of a CNI holiday (a planned temporary switch from a CNI to an mTOR inhibitor to limit exposure to CNIs) lasting no more than 10 days.
10.Known hypersensitivity to sirolimus or its derivatives or macrolide antibiotics.
11.Treatment with voriconazole, cisapride, or ketoconazole, which are all known to interact with sirolimus, that is not discontinued before randomization.
12.Treatment with aminoglycosides, amphotericin B, cisplatin, or other drugs associated with renal dysfunction that is not discontinued before randomization.
13.Subjects with screening baseline white blood cell (WBC) count < 3000/mm3, platelet count < 100,000/mm3, fasting triglyceride level > 400 mg/dL (4.5 mmol/L), or total cholesterol level > 300 mg/dL (7.6 mmol/L).
14.History of malignancy within 3 years before enrollment (except for adequately treated basal-cell or squamous-ell carcinoma of the skin).
15.Planned used of agents with a known major interaction with sirolimus or CNIs.
16.Subjects who are known to be positive for human immunodeficiency virus (HIV).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the superiority of converting from CNI therapy to sirolimus therapy to continuing CNI therapy with respect to renal function in cardiac transplant recipients with mild to moderate renal dysfunction.;Secondary Objective: To evaluate the safety of conversion from CNI therapy to sirolimus therapy in this patient population.<br>To explore the effect of conversion from CNI therapy to sirolimus therapy on surrogate markers of cardiovascular risk.;Primary end point(s): Change from baseline calculated creatinine clearance (using the Cockcroft-Gault equation and adjusted for BSA using the Mosteller formula) at 52 weeks.