Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation
Condition: Disorder Related to Cardiac Transplantation
Intervention: Everolimus; Mycophenolic acid (MPA)/azathioprine (AZA); Calcineurin inhibitors (CNI); Steroids
Intervention description: 0.75-1.5 mg twice daily. At the week 1 visit and thereafter, the dose was adjusted to target blood concentration in the range 3-8 ng/mL.; In the standard CNI arm, all immunosuppressants including (MPA) and azathioprine (AZA) continued unchanged as per local practice.; Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.; Steroid treatment was according to local practice. If steroids were given, the baseline dose of prednisone or equivalent was to be kept unchanged for all treatment groups for the total study duration, unless a medical condition dictated a change.
Intervention MeSH terms: Mycophenolic Acid; Everolimus; Azathioprine; Calcineurin Inhibitors
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 282.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: thoracic transplant recipients; everolimus; immunosuppressants

Summary:

      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.
    

Eligibility criteria:

        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.