Renal Function and Chronic Allograft Vasculopathy Clinical Trial
— SCHEDULEOfficial title:
SCHEDULE - Scandinavian Heart Transplant Everolimus de Novo Study With Early CNI Avoidance
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
| Status | Completed |
| Enrollment | 115 |
| Est. completion date | December 2012 |
| Est. primary completion date | December 2012 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 70 Years |
| Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Denmark | Novartis Investigative Site | Århus N | |
| Denmark | Novartis Investigative Site | Copenhagen | |
| Norway | Novartis Investigative Site | Oslo | |
| Sweden | Novartis Investigative Site | Göteborg | |
| Sweden | Novartis Investigative Site | Linkoping | |
| Sweden | Novartis Investigative Site | Lund |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
Denmark, Norway, Sweden,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Measured Glomerular Filtration Rate (mGFR), 12 Months After Heart Transplantation | 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. | Week 52 | No |
| Secondary | Progression of Chronic Allograft Vasculopathy (CAV) Based on Maximal Intimal Thickness (MIT) From Baseline to Week 52 | 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. | Baseline and week 52 | No |
| Secondary | Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52 | 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. | Baseline and week 52 | No |
| Secondary | Change in Calculated Glomerular Filtration Rate From Pre-transplantation to Week 52 | 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. | Day 1, weeks 7 to 11(baseline) and of week 52 | No |
| Secondary | Calculated Glomerular Filtration Rate From Pre-Transplantation to Week 52 | 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. | Day 1, weeks 7 to 11 and of week 52 | No |
| Secondary | Number of Rejections Leading to Hemodynamic Compromise | Number of all rejections were recorded through the duration of the study with the intent to identify rejections leading to hemodynamic compromise. | 52 weeks | No |
| Secondary | Occurrence of Treatment Failures up to 12 Months After Transplant | Treatment failure was defined as the number of participants who died or lost their graft at any timepoint througout the duration of the study. | 52 weeks | Yes |
| Secondary | Average Level of Protenuria at Week 52 | Proteinuria is measured as the ratio of albumin/creatinine mg/mmol. Measurements were taken from participants urine samples. | 52 weeks | Yes |
| Secondary | Lipid Profile at 12 Months | Total Cholesterol, LDL-Chol, HDL-Chol and TG at week 52. Measurements were taken via participants blood samples. | 52 weeks | No |
| Secondary | Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment | 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). | Pre transplant and 52 weeks | No |
| Secondary | Change in Quality of Life - Euro Quality of Life 5D (EQ-5D) | 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. | Pre transplant and 52 weeks | No |