SCHEDULE - Scandinavian Heart Transplant Everolimus de Novo Study With Early Calcineurin Inhibitor (CNI) Avoidance

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01266148
First received: August 9, 2010
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

A controlled, randomized, open-label, multicenter study evaluating if early initiation of everolimus and early elimination of cyclosporine in de novo heart transplant recipients can improve long-term renal function and slow down the progression of chronic allograft vasculopathy


Condition Intervention Phase
Renal Function and Chronic Allograft Vasculopathy
Drug: Cyclosporine
Drug: Mycophenolate mofetil
Drug: Corticosteroids
Drug: Everolimus
Drug: Anti Thymocyte Globulin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SCHEDULE - Scandinavian Heart Transplant Everolimus de Novo Study With Early CNI Avoidance

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Measured Glomerular Filtration Rate (mGFR), 12 Months After Heart Transplantation [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Measured Glomerular Filtration Rate (mGFR) describes the flow rate of filtered fluid through the kidney. GFR is equal to the clearance rate when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. Participants' urine was used for this assessment at week 52 after heart transplant.


Secondary Outcome Measures:
  • Progression of Chronic Allograft Vasculopathy (CAV) Based on Maximal Intimal Thickness (MIT) From Baseline to Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    The progression of chronic allograft vasculopathy (CAV) was assessed by intravascular ultrasound (IVUS) examinations and measured Maximal Intimal Thickness (MIT)(in mm). A major coronary epicardial artery (preferentially the left-anterior descending coronary artery) was imaged, and the MIT parameters were recorded at baseline and at week 52.

  • Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    the progression of chronic allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) examinations, measured the incidence of CAV (in percent of patients) at baseline and at week 52. Incidence of CAV represents percent of patients having a MIT (maximal intima thickness) > 0.5 mm.

  • Change in Calculated Glomerular Filtration Rate From Pre-transplantation to Week 52 [ Time Frame: Day 1, weeks 7 to 11(baseline) and of week 52 ] [ Designated as safety issue: No ]
    Change in calculated glomerular filtration rate from pre-transplantation to week 52 was calculated according to the Modification of Diet in Renal Disease (MDRD) method. Measurements were taken prior to transplant (day 1), between weeks 7 to 11 and end week 52.

  • Calculated Glomerular Filtration Rate From Pre-Transplantation to Week 52 [ Time Frame: Day 1, weeks 7 to 11 and of week 52 ] [ Designated as safety issue: No ]
    Calculated Glomerular Filtration Rate from pre-transplantation to week 52 was calculated according to the Modification of Diet in Renal Disease (MDRD) method. Measurements were taken prior to transplant (day 1), between weeks 7 to 11 and end of week 52.

  • Number of Rejections Leading to Hemodynamic Compromise [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Number of all rejections were recorded through the duration of the study with the intent to identify rejections leading to hemodynamic compromise.

  • Occurrence of Treatment Failures up to 12 Months After Transplant [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Treatment failure was defined as the number of participants who died or lost their graft at any timepoint througout the duration of the study.

  • Average Level of Protenuria at Week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Proteinuria is measured as the ratio of albumin/creatinine mg/mmol. Measurements were taken from participants urine samples.

  • Lipid Profile at 12 Months [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Total Cholesterol, LDL-Chol, HDL-Chol and TG at week 52. Measurements were taken via participants blood samples.

  • Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment [ Time Frame: Pre transplant and 52 weeks ] [ Designated as safety issue: No ]
    Change in Quality of Life was assessed via the SF-36 (Minnesota Living with Heart Failure questionnaire ([MLHF)]) before transplant surgery and at week 52 of treatment. The SF-36 is a validated, self-administered questionnaire. The questionnaire, which includes 36 questions measures 8 dimensions of health: physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional, and mental health. Scores can be summarized in 2 summary components assessing physical and mental health. Items in each dimension are coded, aggregated, summed, and transformed into a scale ranging from 0 (worse health) to 100 (best health).

  • Change in Quality of Life - Euro Quality of Life 5D (EQ-5D) [ Time Frame: Pre transplant and 52 weeks ] [ Designated as safety issue: No ]
    Change in Quality of Life was assessed via the EQ-5D questionnaire which consists of: EQ-5D-5L descriptive system and EQ Visual Analogue scale (EQ VAS). The EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The patient indicates his/her health state by checking the most appropriate statement. This decision results in a 1-digit number expressing the level selected for that dimension. The digits for 5 dimensions are combined in a 5-digit number describing the respondent's health state. The possible score is 1 to 5 where a lower number indicates improvement. The EQ VAS records the patient's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. The score is 0 to 100 where a higher score represents improvement.


Enrollment: 115
Study Start Date: November 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Drug: Cyclosporine
Cyclosporine (CsA) control group target blood level: 150-350 ng/mL (month 1-3); 100-250 ng/mL (month 4-6); 60-200 ng/mL (month 7-12); everolimus group target blood level: 75-175 ng/mL (month 1-3)
Drug: Mycophenolate mofetil
Mycophenolate mofetil (MMF) target dose for control group: 2000-3000 mg/day everolimus group target dose: 1500-2000 mg/day and 75-175 ng/mL after week 11
Drug: Corticosteroids
Corticosteroids (CS) initiated at 0.2-0.5 mg/kg/day. Tapered to no less than 0.1 mg/kg at Month 3 for control and everolimus groups.
Drug: Everolimus
Everolimus 0.75 mg twice a day as starting dose up to a target blood level: 3-6 ng/mL (7-11 weeks) and 6-10 ng/mL for remaining of study
Drug: Anti Thymocyte Globulin
Induction therapy, Anti Thymocyte Globulin (ATG): 1-2 mg/kg/day during 3-5 days for control and everolimus groups after transplant surgery and prior to randomization.
Experimental: Control
Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Drug: Cyclosporine
Cyclosporine (CsA) control group target blood level: 150-350 ng/mL (month 1-3); 100-250 ng/mL (month 4-6); 60-200 ng/mL (month 7-12); everolimus group target blood level: 75-175 ng/mL (month 1-3)
Drug: Mycophenolate mofetil
Mycophenolate mofetil (MMF) target dose for control group: 2000-3000 mg/day everolimus group target dose: 1500-2000 mg/day and 75-175 ng/mL after week 11
Drug: Corticosteroids
Corticosteroids (CS) initiated at 0.2-0.5 mg/kg/day. Tapered to no less than 0.1 mg/kg at Month 3 for control and everolimus groups.
Drug: Anti Thymocyte Globulin
Induction therapy, Anti Thymocyte Globulin (ATG): 1-2 mg/kg/day during 3-5 days for control and everolimus groups after transplant surgery and prior to randomization.

Detailed Description:

This was a prospective, multi-center, randomized, controlled, parallel group, open label study in de novo heart transplant recipients. Patients eligibility for randomization was assessed 5 days after heart transplant.. Patients fulfilling the inclusion and exclusion criteria were randomized to one of two treatment groups: either conventional treatment with Cyclosporine A (CsA), Mycophenolate mofetil (MMF), and corticosteroids (Group A), or low-dose CsA and everolimus, reduced dose MMF, and corticosteroids (Group B). After 7 to 11 weeks, CsA was discontinued in Group B, while the standard triple-drug immunosuppressive regimen was maintained in Group A.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

De novo heart transplant recipients who had received induction therapy with antithomocyte globulin (ATG) were eligible for inclusion.

Recipients of multi-organ transplants or a previous transplant were excluded, as were those with a donor aged > 70 years, cold ischemia time >6 hours, patients with severe systemic infection, recipients of ABO incompatible transplants, patients with severe hypercholesterolemia (>350mg/dL) or hypertriglyceridemia (>750 mg/dL), patients with past (<5 years). In order to continue in the study after week 7-11 (period 1), patients had to complete first 7-11 weeks on randomized immunosuppression and none of the following criteria should be present: Ongoing rejection treatment or experience of one grade 3R rejection or two or more grade 2R rejections during first 7-11 weeks.

  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: NCT01266148

Locations
Denmark
Novartis Investigative Site
Copenhagen, Denmark, DK-2100
Novartis Investigative Site
Århus N, Denmark, DK-8200
Norway
Novartis Investigative Site
Oslo, Norway, 0424
Sweden
Novartis Investigative Site
Göteborg, Sweden, 413 45
Novartis Investigative Site
Linkoping, Sweden, 581 85
Novartis Investigative Site
Lund, Sweden, 221 85
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: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01266148     History of Changes
Other Study ID Numbers: CRAD001ANO02, 2009-013074-41
Study First Received: August 9, 2010
Results First Received: April 11, 2014
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration
Norway: Norwegian Institute of Public Health

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Antilymphocyte Serum
Cyclosporine
Cyclosporins
Everolimus
Mycophenolate mofetil
Mycophenolic Acid
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014