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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00377962
First received: September 15, 2006
Last updated: May 12, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Disorder Related to Cardiac Transplantation
Drug: Everolimus
Drug: Mycophenolic acid (MPA)/azathioprine (AZA)
Drug: Calcineurin inhibitors (CNI)
Drug: Steroids
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation: Results at 24 Months

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
    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.

  • Change in Serum Creatinine From Baseline to End of Study (Month 24) [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
    Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function.

  • Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24) [ Time Frame: Month 12 to end of study (Month 24) ] [ Designated as safety issue: No ]
    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.

  • Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) [ Time Frame: Month 12 to end of study (Month 24) ] [ Designated as safety issue: No ]
    Number of patients not alive and number of patients with loss of their graft.

  • Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) [ Time Frame: Month 12 to end of study (Month 24) ] [ Designated as safety issue: No ]
  • Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
    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.

  • Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
    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.

  • Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
    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.

  • Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
    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.

  • Mean Days of Hospitalization From Baseline to End of Study (Month 24) [ Time Frame: Baseline to end of study (Month 24) ] [ Designated as safety issue: No ]
  • Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) [ Time Frame: Month 12 to end of study (Month 24) ] [ Designated as safety issue: Yes ]

Enrollment: 282
Study Start Date: December 2005
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + CNI reduction
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.
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.
Other Name: Certican
Drug: Calcineurin inhibitors (CNI)
Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.
Drug: 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.
Active Comparator: Control
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.
Drug: Mycophenolic acid (MPA)/azathioprine (AZA)
In the standard CNI arm, all immunosuppressants including (MPA) and azathioprine (AZA) continued unchanged as per local practice.
Other Name: Neoral®/Prograf®
Drug: Calcineurin inhibitors (CNI)
Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00377962

Locations
Denmark
Novartis Investigative Site
Arhus, Denmark, DK-8200
Novartis Investigative Site
Copenhagen, Denmark, 2100
Norway
Novartis Investigative Site
Oslo, Norway
Sweden
Novartis Investigative Site
Goteborg, Sweden, 413 45
Novartis Investigative Site
Linkoping, Sweden, 581 85
Novartis Investigative Site
Lund, Sweden, 22185
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis Pharmaceticals
ClinicalTrials.gov Identifier: NCT00377962     History of Changes
Other Study ID Numbers: CRAD001AIC01
Study First Received: September 15, 2006
Results First Received: March 23, 2011
Last Updated: May 12, 2011
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Novartis:
thoracic transplant recipients
everolimus
immunosuppressants

Additional relevant MeSH terms:
Azathioprine
Immunosuppressive Agents
Mycophenolate mofetil
Everolimus
Sirolimus
Mycophenolic Acid
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Enzyme Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 01, 2014