Clinical trial NCT00377962: Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation
Official title: Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation: Results at 24 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Cardiac Transplantation
Keywords: thoracic transplant recipients
everolimus
immunosuppressants
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-09-19
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Primary outcomes:
measure: Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12
timeFrame: Baseline to Month 12
Secondary outcomes:
measure: Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24)
timeFrame: Baseline to end of study (Month 24)
measure: Change in Serum Creatinine From Baseline to End of Study (Month 24)
timeFrame: Baseline to end of study (Month 24)
measure: Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24)
timeFrame: Month 12 to end of study (Month 24)
measure: Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24)
timeFrame: Month 12 to end of study (Month 24)
measure: Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24)
timeFrame: Month 12 to end of study (Month 24)
measure: Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup
timeFrame: Baseline to end of study (Month 24)
measure: Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup
timeFrame: Baseline to end of study (Month 24)
measure: Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup
timeFrame: Baseline to end of study (Month 24)
measure: Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup
timeFrame: Baseline to end of study (Month 24)
measure: Mean Days of Hospitalization From Baseline to End of Study (Month 24)
timeFrame: Baseline to end of study (Month 24)
measure: Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24)
timeFrame: Month 12 to end of study (Month 24)
Other outcomes:
Locations:
city: Arhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Linkoping
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Norum HM, Michelsen AE, Lekva T, Arora S, Otterdal K, Olsen MB, Kong XY, Gude E, Andreassen AK, Solbu D, Karason K, Dellgren G, Gullestad L, Aukrust P, Ueland T. Circulating delta-like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus-based immunosuppression. Am J Transplant. 2019 Apr;19(4):1050-1060. doi: 10.1111/ajt.15141. Epub 2018 Nov 5.
citation: Arora S, Erikstad I, Ueland T, Sigurdardottir V, Ekmehag B, Jansson K, Eiskjaer H, Botker HE, Mortensen SA, Saunamaki K, Gude E, Ragnarsson A, Solbu D, Aukrust P, Gullestad L. Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial. Am J Transplant. 2012 Oct;12(10):2700-9. doi: 10.1111/j.1600-6143.2012.04234.x. Epub 2012 Sep 7.
citation: Arora S, Gude E, Sigurdardottir V, Mortensen SA, Eiskjaer H, Riise G, Mared L, Bjortuft O, Ekmehag B, Jansson K, Simonsen S, Aukrust P, Solbu D, Iversen M, Gullestad L. Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: the significance of baseline glomerular filtration rate. J Heart Lung Transplant. 2012 Mar;31(3):259-65. doi: 10.1016/j.healun.2011.12.010.