Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation (NOCTET)

Novartis

Status and phase: Completed; Phase 4

Conditions: Disorder Related to Cardiac Transplantation

Treatments: Drug: Steroids; Drug: Calcineurin inhibitors (CNI); Drug: Mycophenolic acid (MPA)/azathioprine (AZA); Drug: Everolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00377962

CRAD001AIC01

Details and patient eligibility

About

This study investigated whether initiation of everolimus together with reduction of calcineurin inhibitors (CNI) in maintenance heart or lung transplant patients with renal impairment would improve renal function.

Enrollment: 282 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients who have undergone a heart or lung transplantation more than 12 months ago.
• Patients receiving Neoral® or Prograf®.
• Patients with a measured or calculated glomerular filtration rate (GFR) > 20 and < 70 mL/min/1.73m^2. For patients with a GFR > 60 and < 70 mL/min/1.73m^2, a deteriorated renal function since the time of transplantation must be documented by at least one post-transplant GFR level that is > 10% above the GFR level at the time of inclusion.
• Patients willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months.
• Females of potential childbearing age must have a negative serum pregnancy test within 7 days prior to enrollment. Effective contraception must be used during the trial and for 6 weeks following discontinuation of the study medication, even where there has been a history of infertility.

Exclusion criteria

• Patients who are recipients of multiple organ transplants.
• Patients with measured GFR < 20 mL/min/1.73m^2 or > 70 mL/min/1.73m^2.
• Patients with a treated acute rejection episode within the last 3 months.
• Patients with a platelet count of < 50,000/mm^3 or with a white blood cell count of ≤ 2,500/mm^3 or with a hemoglobin value < 8 g/dL.
• Presence of severe hypercholesterolemia (≥ 8.0 mmol/L) or hypertriglyceridemia (≥ 6.0 mmol/L) despite conventional lipid lowering treatment.
• Patients currently treated or who have been treated with a mammalian target of rapamycin (mTOR) inhibitor.
• Patients who have received an investigational drug within 4 weeks.
• Patients who are human immunodeficiency virus positive or who have a current severe systemic infection requiring continued therapy according to investigator judgment.
• Present use of any immunosuppressive drugs other than Neoral®/Prograf®, mycophenolic acid/azathioprine (MPA/AZA), and/or steroids.
• Patients with a known hypersensitivity to drugs similar to everolimus.
• Symptoms of significant mental illness which, in the opinion of the investigator, may interfere with the patient's ability to comply with the protocol. History of drug or alcohol abuse within 1 year of baseline.
• Inability to cooperate or communicate with the investigator.
• Patients with any past (within the last 5 years) or present malignancy other than excised squamous or basal cell carcinoma.
• Females of childbearing potential that are planning to become pregnant, who are pregnant and/or lactating, or who are unwilling to use effective means of contraception.
• Patients with a planned coronary revascularization or patients who have experienced a major adverse cardiovascular event (MACE) within the last 3 months.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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282 participants in 2 patient groups

Everolimus + CNI reduction

Experimental group

Description:

Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice.

Treatment:

Drug: Everolimus

Drug: Calcineurin inhibitors (CNI)

Drug: Steroids

Control

Active Comparator group

Description:

CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice.

Treatment:

Drug: Mycophenolic acid (MPA)/azathioprine (AZA)

Drug: Calcineurin inhibitors (CNI)

Drug: Steroids