Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation

Disorder Related to Cardiac Transplantation Clinical Trial

— NOCTET  

Official title:

Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation: Results at 24 Months

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00377962
• Other study ID #: CRAD001AIC01
• Status: Completed
• Phase: Phase 4
• Start date: December 2005
• Est. completion date: February 2010

Study information

• Verified date: July 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disorder Related to Cardiac Transplantation

Intervention

Drug:
• Everolimus
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.
• Mycophenolic acid (MPA)/azathioprine (AZA)
In the standard CNI arm, all immunosuppressants including (MPA) and azathioprine (AZA) continued unchanged as per local practice.
• Calcineurin inhibitors (CNI)
Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.
• Steroids
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.

Locations

Country	Name	City	State
Denmark	Novartis Investigative Site	Arhus
Denmark	Novartis Investigative Site	Copenhagen
Norway	Novartis Investigative Site	Oslo
Sweden	Novartis Investigative Site	Goteborg
Sweden	Novartis Investigative Site	Linkoping
Sweden	Novartis Investigative Site	Lund

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12	Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.	Baseline to Month 12
Secondary	Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24)	Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.	Baseline to end of study (Month 24)
Secondary	Change in Serum Creatinine From Baseline to End of Study (Month 24)	Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function.	Baseline to end of study (Month 24)
Secondary	Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24)	Biopsy-proved acute rejection was defined as a treated acute rejection confirmed by biopsy, graded locally according to the International Society for Heart & Lung Transplantation (ISHLT) criteria. A treated acute rejection was defined as an acute rejection clinically suspected, whether biopsy-proven or not, which had been treated and confirmed by the investigator according to the response to therapy.	Month 12 to end of study (Month 24)
Secondary	Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24)	Number of patients not alive and number of patients with loss of their graft.	Month 12 to end of study (Month 24)
Secondary	Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24)		Month 12 to end of study (Month 24)
Secondary	Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup	Forced expiratory volume in 1 second (FEV1) was measured by spirometry conducted according to internationally accepted standards. FEV1 is the volume delivered in the first second of a forced vital capacity (FVC) maneuver. A positive change score indicates improved lung function.	Baseline to end of study (Month 24)
Secondary	Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup	Forced vital capacity (FVC) was measured by spirometry conducted according to internationally accepted standards. FVC is the volume delivered during an expiration made as forcefully and completely as possible starting from full inspiration. A positive change score indicates improved lung function.	Baseline to end of study (Month 24)
Secondary	Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup	Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal wall thickness (IVSTd), and posterior wall thickness (PWTd). A positive change score indicates improved left ventricular function.	Baseline to end of study (Month 24)
Secondary	Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup	Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were filling fraction (FF) and ejection fraction (EF). A positive change score indicates improved left ventricular function.	Baseline to end of study (Month 24)
Secondary	Mean Days of Hospitalization From Baseline to End of Study (Month 24)		Baseline to end of study (Month 24)
Secondary	Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24)		Month 12 to end of study (Month 24)