Liver TransplantationPhase 3NCT00378014
Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy
A Phase 3 study testing everolimus, basiliximab and CNI in people with Liver Transplantation, run by Novartis Pharmaceuticals at 16 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- everolimus, basiliximab and CNI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 276 participants
- Where
- 16 sitesin 4 countries
- Study dates
- Aug 2006to Jan 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females 18 - 70 years old
- Liver transplant recipient (living or deceased donor)
- Patients in whom an allograft biopsy will not be contraindicated
Who cannot join
- 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)
Show all 9Show fewer
- 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.
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
Germany10 sites
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Regensburg, 93053
Novartis Investigative Site
Tübingen, 72076
Austria2 sites
Novartis Investigative Site
Innsbruck, A-6020
Novartis Investigative Site
Vienna, A-1090
Netherlands2 sites
Novartis Investigative Site
Groningen, 9713 GZ
Novartis Investigative Site
Rotterdam, 3015 CE
Switzerland2 sites
Novartis Investigative Site
Geneva, 1211
Novartis Investigative Site
Zurich, Switzerland, 8091
About this study
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
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.
- Conditions
- Liver Transplantation
- Being tested
- everolimus, basiliximab, CNI
- Keywords
- Liver transplantation, everolimus, CNI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called certican
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.
basiliximabDrug
Also called simulect
All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.
CNIDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Basiliximab plus everolimus-based immunosuppressive regimen following the reduction and cessation of initial CNI regimen plus optional steroids according to local best practice Receives: Drug: basiliximab; Drug: CNI |
| Calcineurin Inhibitor (CNI) | Active comparator | Basiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice Receives: Drug: everolimus; Drug: basiliximab; Drug: CNI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calculated Glomerular Filtration Rate (cGFR)
This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.
Measured: Month 11
Secondary outcomes (9)
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).
Measured: Month 11
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).
Measured: Month 11
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.
Measured: Baseline, Month 11
Renal Function (cGFR)
This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.
Measured: Month 5
Incidence of Treated BPAR
The incidence of treated BPAR was estimated using crude rate estimation (relative frequency).
Measured: Month 11
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.
Measured: Month 11
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).
Measured: Baseline, Month 5
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.
Measured: From randomization to Month 11
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.
Measured: Month 12 to Month 59 post-baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2006 (estimated)
- Study startAug 2006
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 276 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00378014
- Sponsor's protocol ID
- CRAD001HDE10
- Other IDs
- 2005-002920-32, 2005
- Status last verified
- Jan 2015
- First submitted
- 15 Sep 2006
- Last updated
- 6 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00378014
- Acronym / sponsor ID
- CRAD001HDE10
- Conditions
- Liver Transplantation
- Keywords
- Liver transplantation, everolimus, CNI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 276 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 19 Sep 2006 (estimated)
- Results
- Posted 3 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: basiliximab, Drug: CNIBasiliximab plus everolimus-based immunosuppressive regimen following the reduction and cessation of initial CNI regimen plus optional steroids according to local best practice |
| Calcineurin Inhibitor (CNI) | Active comparator | Drug: everolimus, Drug: basiliximab, Drug: CNIBasiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males or females 18 - 70 years old
- Liver transplant recipient (living or deceased donor)
- Patients in whom an allograft biopsy will not be contraindicated
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: certicanStart 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. | Drug | Calcineurin Inhibitor (CNI) |
| basiliximabAlso: simulectAll patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4. | Drug | Calcineurin Inhibitor (CNI), Everolimus |
| CNIPatients 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. | Drug | Calcineurin Inhibitor (CNI), Everolimus |
Primary outcome
Calculated Glomerular Filtration Rate (cGFR)
Time frame: Month 11
This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.
9 secondary outcomes
Incidence of Efficacy Failure
Time frame: Month 11
Incidence of the Need for a Change in the Immunosuppressive Regimen
Time frame: Month 11
Incidence of Renal Deterioration
Time frame: Baseline, Month 11
Renal Function (cGFR)
Time frame: Month 5
Incidence of Treated BPAR
Time frame: Month 11
Patient and Graft Survival
Time frame: Month 11
Hepatitis C Virus (HCV) Replication in HCV-positive Patients
Time frame: Baseline, Month 5
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Time frame: From randomization to Month 11
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Time frame: Month 12 to Month 59 post-baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Liver Transplantation
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
RecruitingPhase 2
Expanding Liver Transplant Immunosuppression Minimization Via Everolimus
Liver Transplant
RecruitingObservational study
Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing everolimus, basiliximab and CNI in people with Liver Transplantation, run by Novartis Pharmaceuticals at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany, Austria, Netherlands, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calculated Glomerular Filtration Rate (cGFR) (time frame: Month 11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2015.