Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy

Liver Transplantation Clinical Trial

Official title:

Presentation of Renal Function in Liver Transplant Recipients With Certican Therapy: PROTECT Study A Twelve-month, Multicenter, Randomized, Open-label Study of Safety, Tolerability and Efficacy of Certican-based Regimen Versus Calcineurin Inhibitor-based Regimen in de Novo Liver Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00378014
• Other study ID #: CRAD001HDE10
• Secondary ID: 2005-002920-32
• Status: Completed
• Phase: Phase 3
• First received: September 15, 2006
• Last updated: January 19, 2015
• Start date: August 2006
• Est. completion date: January 2013

Study information

• Verified date: January 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

The study is designed to show that everolimus initiation together with reduction and thereafter discontinuation of calcineurin inhibitor (CNI) will improve significantly renal function in de novo liver transplant recipients as compared to continuation of CNI-based treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Males or females 18 - 70 years old

• Liver transplant recipient (living or deceased donor)

• Patients in whom an allograft biopsy will not be contraindicated

Exclusion Criteria:

• Recipients of multiple solid organ transplants or patients that have already received a transplant in the past

• HCV positive patients who need an active anti-viral treatment (HCV- positive patients without active antiviral treatment are allowed)

• HIV positive patients

• Patients who are breast feeding

• Patients with a current severe systemic infection

• Presence of any hypersensitivity to drugs similar to Certican® (e.g. macrolides)

• Preexisting (i.e. not related to CNI-damage) renal dysfunction that, according to the judgment of the investigator, will not significantly improve after transplantation (i.e., for example, patients that are expected to have a cGFR below 50ml/min at 4 weeks post transplantation)

• Patients that have received Simulect prior to this study.

• Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• everolimus
Start dose of everolimus was 1.5 mg in the morning followed by 1.5 mg in the evening. After one week, the dose was adjusted to achieve trough levels between 5-12 ng/mL. Once trough levels were above 5ng/mL, the CNI dose was reduced to 70%. At week 8 post-baseline (latest at week 16 post baseline), CNI was completely discontinued. For patients receiving Ciclosporin A (CiA) as CNI, the everolimus dosage was adjusted to achieve a trough level of 8-12 ng/mL, prior to discontinuation of CiA. After discontinuation of CNI, everolimus was maintained at a trough level of 5-12 ng/mL.
• basiliximab
All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.
• CNI
Patients who met the screening eligibility received CNI-based immunosuppressive therapy for 1 month. Then at week 4 (or week 8 at maximum), patients randomized to the CNI arm continued on CNI-based immunosuppressive therapy.

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Wien
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Tübingen
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Switzerland	Novartis Investigative Site	Genève
Switzerland	Novartis Investigative Site	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Calculated Glomerular Filtration Rate (cGFR)	This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.	Month 11	No
Secondary	Incidence of Efficacy Failure	Efficacy failure was defined as the composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, death, lost to follow-up (from any reason), whichever occurred first. Incidence of efficacy failure was estimated using crude rate estimation (relative frequency).	Month 11	No
Secondary	Incidence of the Need for a Change in the Immunosuppressive Regimen	The incidence of any changes in the immunosuppressive regimen other than allowed in the study protocol (for example, introduction of Mycophenolic acid (MPA) or sirolimus) was estimated using crude rate estimation (relative frequency).	Month 11	No
Secondary	Incidence of Renal Deterioration	Renal deterioration was defined as a decrease by =25% in the cGFR compared to baseline and confirmed by one consecutive measurement. The analysis of this outcome measure was omitted because of missing relevance.	Baseline, Month 11	No
Secondary	Renal Function (cGFR)	This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.	Month 5	No
Secondary	Incidence of Treated BPAR	The incidence of treated BPAR was estimated using crude rate estimation (relative frequency).	Month 11	No
Secondary	Patient and Graft Survival	Patient survival was defined as the time from date of randomization to date of death from any cause. If a patient was not known to have died, patient survival was censored as the date of last contact. Graft survival was defined as the time from the date of randomization to the date of graft loss. If a patient was not known to suffer from a graft loss or died without graft loss, time to graft loss was censored with date of last contact or date of death, respectively. Patient and graft survival were analyzed using the Kaplan Meier method.	Month 11	No
Secondary	Hepatitis C Virus (HCV) Replication in HCV-positive Patients	HCV ribonucleic acid (RNA) was measured by real time reverse transcriptase polymerase chain reaction (PCR; copies per mL).	Baseline, Month 5	No
Secondary	Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death	Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.	From randomization to Month 11	Yes
Secondary	Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death	Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.	Month 12 to Month 59 post-baseline	Yes