Clinical trial NCT01404325: Efficacy Regarding Renal Function of Everolimus in Combination With Specific Standard Immunosuppressive Regimen Lung Transplant Recipients
Official title: A 2-arm, Prospective, Randomized, Controlled, Open-label, 12 Month Phase III Trial to Evaluate the Efficacy Regarding Renal Function of Everolimus in Combination With a Centre Specific Standard Immunosuppressive Regimen Consisting of CNI, Purinantagonists and Steroids Versus a Standard Triple Immunosuppressive Regimen in Lung Transplant Recipients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Transplantation
Keywords: Lung transplantation
everolimus
kidney function
renal function
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-07-28
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial evaluated the efficacy of an everolimus-based quadruple low immunosuppressive regimen versus a standard immunosuppressive regimen concerning kidney function in lung transplant recipients.


Eligibility criteria: Inclusion criteria:

* Adult recipients of de novo cadaveric lung transplants 3-18 months prior to enrollment

Exclusion criteria:

* Patients with thrombocytopenia (platelets \<100,000/mm³), with an absolute neutrophil count of \<1,500/mm³ or leucopenia (leucocytes \<3000/mm³), with anemia with Hb \< 8g/dl at time of screening
* Patients with uncontrolled hypercholesterolemia (\> 350 mg/dL; \> 9.1 mmol/L) or hypertriglyceridemia (\> 750 mg/dL; \> 8.5 mmol/L) at time of screening
* Patients with a history of malignancy of any organ system, treated or untreated, during the last five years, whether or not there is evidence of local recurrence or metastases, except squamous or basal cell carcinoma of the skin Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 Months
timeFrame: Month 12
Secondary outcomes:
measure: Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Calculated Glomerular Filtration Rate (cGFR) According to Cystatin C-based Hoek's Formula at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Incidence of Patients Experiencing a Decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/Min From Baseline to Month 6 and 12.
timeFrame: Baseline, Month 6, Month 12
measure: Incidence of Renal Replacement Therapy at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Time to Renal Replacement Therapy at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Incidence of Acute Rejection Episodes at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Incidence of Graft Loss/Re-transplantation at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Incidence of Bronchiolitis Obliterans Syndrome (BOS) at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Incidence of Death at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Quality of Life (QoL, SF36) at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Exercise Capacity 6-Minute Walk Test(6MWT) at Month 6 and Month 12
timeFrame: Month 6, Month 12
measure: Incidence of Treated Arterial Hypertension up to Month 12
timeFrame: up to Month 12
measure: Incidence of Diabetes Mellitus up to Month 12
timeFrame: up to Month 12
measure: Trough Levels of Everolimus at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Adherence to Target Ranges of Everolimus at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Trough Levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Adherence to Target Ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Trough Levels of Tacrolimus at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Adherence to Target Ranges of Tacrolimus at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Incidence of Bacterial, Viral, and Fungal Infections at Month 12
timeFrame: Month 12
measure: Triglyceride Levels at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Total Cholesterol Levels at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: Low-Density Lipoprotein (LDL)Cholesterol Levels at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
measure: High-Density Lipoprotein (HDL)Cholesterol Levels at Month 1, 3, 6, 9, 12
timeFrame: Month 1, 3, 6, 9, 12
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmceuticals
role: STUDY_DIRECTOR
References:
citation: Kneidinger N, Valtin C, Hettich I, Frye BC, Wald A, Wilkens H, Bessa V, Gottlieb J. Five-year Outcome of an Early Everolimus-based Quadruple Immunosuppression in Lung Transplant Recipients: Follow-up of the 4EVERLUNG Study. Transplantation. 2022 Sep 1;106(9):1867-1874. doi: 10.1097/TP.0000000000004095. Epub 2022 Mar 8.
citation: Gottlieb J, Neurohr C, Muller-Quernheim J, Wirtz H, Sill B, Wilkens H, Bessa V, Knosalla C, Porstner M, Capusan C, Struber M. A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation. Am J Transplant. 2019 Jun;19(6):1759-1769. doi: 10.1111/ajt.15251. Epub 2019 Feb 5.