Efficacy of Everolimus in Combination With Tacrolimus in Liver Transplant Recipients
HEPHAISTOS
A 12-month, Multi-center, Open-label, Randomized, Controlled Study to Evaluate Efficacy/Safety and Evolution of Renal Function of Everolimus in Co-exposure With Tacrolimus in de Novo Liver Transplant Recipients
2 other identifiers
interventional
339
1 country
15
Brief Summary
This trial evaluated the efficacy and safety of Everolimus in combination with tacrolimus versus a standard immunosuppressive regimen concerning kidney function in liver transplant recipients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started May 2012
Longer than P75 for phase_4
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 8, 2012
CompletedFirst Posted
Study publicly available on registry
March 12, 2012
CompletedStudy Start
First participant enrolled
May 24, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 8, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 8, 2017
CompletedResults Posted
Study results publicly available
May 10, 2019
CompletedMay 10, 2019
May 1, 2019
5.2 years
March 8, 2012
August 2, 2018
May 9, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Estimated Glomerular Filtration Rate (GFR)
The estmated GFR was calculated using MDRD-4 formula (Modification of Diet in Renal Disease Study Group).
month 12
Secondary Outcomes (6)
Estimated GFR - PP Set
month 12
Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death
12 months
Number of Participants With HCV
12 months
Incidence of HCV Related Fibrosis
12 months
Incidence of de Novo HCC Malignancies
12 months
- +1 more secondary outcomes
Study Arms (2)
EVR/TAC
EXPERIMENTALTacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)
TAC
ACTIVE COMPARATORTacrolimus (C0-h: 6-10 ng/ml)
Interventions
tablet containing 0.25mg, 0.5mg, 0.75mg or 1.0mg
For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids may have been used for the duration of the study according to the investigator's discretion, but may not have been eliminated sooner than 6 months post-transplantation.
Eligibility Criteria
You may qualify if:
- Male or female recipients of a full-size liver allograft, aged 18 to 65 years.
You may not qualify if:
- Patients with thrombocytopenia (platelets \<50,000/mm³), with an absolute neutrophil count of \<1,000/mm³ or leucopenia (leucocytes \<2000/mm³), with anemia with Hb \< 6g/dl at time of randomization
- Patients with uncontrolled hypercholesterolemia (\>350mg/dL; \>9mmol/L) or hypertriglyceridemia (\>750 mg/dL; \>8.5 mmol/L) at time of randomization
- History of malignancy of any organ system within the past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Novartis Investigative Site
Aachen, 52074, Germany
Novartis Investigative Site
Berlin, 13353, Germany
Novartis Investigative Site
Bonn, 53105, Germany
Novartis Investigative Site
Erlangen, 91052, Germany
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Frankfurt, 60590, Germany
Novartis Investigative Site
Hamburg, 20246, Germany
Novartis Investigative Site
Hanover, 30625, Germany
Novartis Investigative Site
Heidelberg, 69120, Germany
Novartis Investigative Site
Kiel, 24105, Germany
Novartis Investigative Site
Leipzig, 04103, Germany
Novartis Investigative Site
Mainz, 55131, Germany
Novartis Investigative Site
München, 81377, Germany
Novartis Investigative Site
Regensburg, 93053, Germany
Novartis Investigative Site
Tübingen, 72076, Germany
Related Publications (2)
Nashan B, Schemmer P, Braun F, Schlitt HJ, Pascher A, Klein CG, Neumann UP, Kroeger I, Wimmer P; Hephaistos Study Group. Early Everolimus-Facilitated Reduced Tacrolimus in Liver Transplantation: Results From the Randomized HEPHAISTOS Trial. Liver Transpl. 2022 Jun;28(6):998-1010. doi: 10.1002/lt.26298. Epub 2021 Oct 12.
PMID: 34525259DERIVEDNashan B, Schemmer P, Braun F, Dworak M, Wimmer P, Schlitt H. Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial. Trials. 2015 Mar 26;16:118. doi: 10.1186/s13063-015-0626-0.
PMID: 25873064DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2012
First Posted
March 12, 2012
Study Start
May 24, 2012
Primary Completion
August 8, 2017
Study Completion
August 8, 2017
Last Updated
May 10, 2019
Results First Posted
May 10, 2019
Record last verified: 2019-05