Liver TransplantationPhase 3NCT00149890
Efficacy and Safety of Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients Avoiding Intraoperative Steroids
A Phase 3 study testing Basiliximab, Cyclosporine/cyclosporine microemulsion and Steroid in people with Liver Transplantation and Infection, run by Novartis at 1 site in Germany.
Trial summary
Systemic infection is still a major concern in young children with liver transplantation. The approach of this study is to reduce the risk of systemic infections by avoiding intraoperative steroids (another class of immunosuppressive drugs) given in combination with basiliximab, cyclosporine and steroids in pediatric… Read more about this study
- Who is it for?
- Ages Up to 16 years
- Conditions the study is for
- Liver Transplantation, Infection
- What is being tested?
- Basiliximab, Cyclosporine/cyclosporine microemulsion and Steroid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2004to Mar 2009
- 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 Up to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Pediatric patients undergoing primary orthotopic liver transplantation (whole organ or split liver or reduced size)
- Cadaveric or living donor (related or unrelated)
Who cannot join
- Patients who are recipients of multiple solid organ transplants and/or who have previously received transplanted organs
- If cold ischemia time of the transplanted organ is >12 hours
- Auxiliary liver transplant recipients
- Fulminant hepatic failure
- Autoimmune hepatitis
- Primary sclerosing cholangitis
Show all 15Show fewer
- Severe acute systemic infections
- Hepatitis B surface antigen/HCV/HIV positive
- Known contraindication to intravenous (i.v.) or per os (orally) (p.o.) cyclosporine or corticoids
- Non-ability to comply with the protocol
- Relevant abnormal physical or laboratory findings within 2 weeks of inclusion
- Relevant severe allergy, hypersensitivity to basiliximab or similar drugs
- History/presence of relevant malignancy
- Pregnancy/breastfeeding
- Use of any investigational or immunomodulatory/immunosuppressive drug within 4 weeks prior to transplantation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter, Open-label, Randomized, Two Arm Study to Investigate the Efficacy and Safety of a Therapy Avoiding Intraoperative Steroids in Combination With Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients
Systemic infection is still a major concern in young children with liver transplantation. The approach of this study is to reduce the risk of systemic infections by avoiding intraoperative steroids (another class of immunosuppressive drugs) given in combination with basiliximab, cyclosporine and steroids in pediatric de novo liver transplant recipients. The treatment is compared to the same treatment regimen including intraoperative steroids with respect to rejection episodes.
- Conditions
- Liver Transplantation, Infection
- Being tested
- Basiliximab, Cyclosporine/cyclosporine microemulsion, Steroid
- Keywords
- pediatric, liver transplantation, Simulect, Basiliximab, ciclosporin microemulsion, steroid reduction, pediatric liver transplantation
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BasiliximabDrug
Also called Simulect®
Basiliximab (10 mg) was supplied as a lyophilisate in vials with ampoules of sterile water for injection (5 mL) and had to be given of 10 mg (body weight <35 kg) or 20 mg (body weight ≥35 kg) strength.
Cyclosporine/cyclosporine microemulsionDrug
Also called Sandimmun®/Sandimmun® Optoral
Cyclosporine/cyclosporine microemulsion had to be started with 100 mg/m²/day intravenous (i.v) (2x4h) for 7 days and was to be continued i.v. or orally from day 8 onwards as per center practice. During the 6 months treatment period Cyclosporine doses had to be adjusted according to Cyclosporine A (CsA)-trough levels.
SteroidDrug
Intravenous prednisolone (loading dose: 300 mg/m2, maximum 500 mg) had to be administered intraoperatively only in treatment arm 1 (day 0). The first dose of steroids in treatment arm 2 (day 0) had to be administered within 8 hours after reperfusion of the graft. Beginning from day 1 to day 6 doses of 15 mg/m2/day had to be given intravenously (i.v.) in both treatment arms. Then, the steroid doses (oral prednisone or its equivalent) were to be decreased from 10 mg/m²/day orally (day 7-13), to 7.5 mg/m²/day orally (day 14-30), to 4 mg/m²/day orally (until end of month 2), to 2.5 mg/m²/day orally (until end of month 3) and to 1 mg/m²/day orally (until end of month 6).
| Study group | Role | What they receive |
|---|---|---|
| With Intraoperative Steroids | Experimental | Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft. Receives: Drug: Basiliximab; Drug: Cyclosporine/cyclosporine microemulsion; Drug: Steroid |
| Without Intraoperative Steroids | Active comparator | No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection. Receives: Drug: Basiliximab; Drug: Cyclosporine/cyclosporine microemulsion; Drug: Steroid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation
Graft loss is defined as being listed for a re-transplantation. The analysis was based on the locally performed biopsy assessments. Generally, patients not experiencing a relevant event (i.e., acute rejection, graft loss or death) were censored with the last visit date.
Measured: 3 months after treatment
Secondary outcomes (6)
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three Months
At biopsy of transplanted tissue sample, acute rejection has an onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever, and hypertension.
Measured: 3 months
Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six Months
To evaluate the efficacy of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the incidence of steroid resistant rejection episodes within three and six months.
Measured: 3 and 6 months
Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation
Graft loss is defined as being listed for a re-transplantation.
Measured: 3 months and 6 months
Number of Participants With Bacterial, Viral and Fungal Infections During Six Months
To evaluate the safety of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the episodes of bacterial, viral and fungal infections during six months.
Measured: 6 months
Time of Onset of a First Biopsy Proven Acute Rejection
Biopsied Tissue shows rejection at onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever and hypertension
.
Measured: 6 months
Percentage of Participants With Treatment Failure Within Three and Six Months
To evaluate the proportion of patients with treatment failure treated with a therapy consisting of intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids within three and six months.
Measured: 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2005 (estimated)
- Study startMar 2004
- Primary completionMar 2009
- Study completionMar 2009
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.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00149890
- Sponsor's protocol ID
- CCHI621ADE04
- Status last verified
- Aug 2011
- First submitted
- 6 Sep 2005
- Last updated
- 22 Sep 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Randomized, Two Arm Study to Investigate the Efficacy and Safety of a Therapy Avoiding Intraoperative Steroids in Combination With Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients
- ClinicalTrials.gov ID
- NCT00149890
- Acronym / sponsor ID
- CCHI621ADE04
- Conditions
- Liver Transplantation, Infection
- Keywords
- pediatric, liver transplantation, Simulect, Basiliximab, ciclosporin microemulsion, steroid reduction, pediatric liver transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Mar 2004
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 8 Sep 2005 (estimated)
- Results
- Posted 22 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Systemic infection is still a major concern in young children with liver transplantation. The approach of this study is to reduce the risk of systemic infections by avoiding intraoperative steroids (another class of immunosuppressive drugs) given in combination with basiliximab, cyclosporine and steroids in pediatric de novo liver transplant recipients. The treatment is compared to the same treatment regimen including intraoperative steroids with respect to rejection episodes.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| With Intraoperative Steroids | Experimental | Drug: Basiliximab, Drug: Cyclosporine/cyclosporine microemulsion, Drug: SteroidIntraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft. |
| Without Intraoperative Steroids | Active comparator | Drug: Basiliximab, Drug: Cyclosporine/cyclosporine microemulsion, Drug: SteroidNo intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection. |
Who may qualify
- Ages
- Up to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Pediatric patients undergoing primary orthotopic liver transplantation (whole organ or split liver or reduced size)
- Cadaveric or living donor (related or unrelated)
Key exclusion criteria (15 listed)
- Patients who are recipients of multiple solid organ transplants and/or who have previously received transplanted organs
- If cold ischemia time of the transplanted organ is >12 hours
- Auxiliary liver transplant recipients
- Fulminant hepatic failure
- Autoimmune hepatitis
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 |
|---|---|---|
| BasiliximabAlso: Simulect®Basiliximab (10 mg) was supplied as a lyophilisate in vials with ampoules of sterile water for injection (5 mL) and had to be given of 10 mg (body weight <35 kg) or 20 mg (body weight ≥35 kg) strength. | Drug | With Intraoperative Steroids, Without Intraoperative Steroids |
| Cyclosporine/cyclosporine microemulsionAlso: Sandimmun®/Sandimmun® OptoralCyclosporine/cyclosporine microemulsion had to be started with 100 mg/m²/day intravenous (i.v) (2x4h) for 7 days and was to be continued i.v. or orally from day 8 onwards as per center practice. During the 6 months treatment period Cyclosporine doses had to be adjusted according to Cyclosporine A (CsA)-trough levels. | Drug | With Intraoperative Steroids, Without Intraoperative Steroids |
| SteroidIntravenous prednisolone (loading dose: 300 mg/m2, maximum 500 mg) had to be administered intraoperatively only in treatment arm 1 (day 0). The first dose of steroids in treatment arm 2 (day 0) had to be administered within 8 hours after reperfusion of the graft. Beginning from day 1 to day 6 doses of 15 mg/m2/day had to be given intravenously (i.v.) in both treatment arms. Then, the steroid doses (oral prednisone or its equivalent) were to be decreased from 10 mg/m²/day orally (day 7-13), to 7.5 mg/m²/day orally (day 14-30), to 4 mg/m²/day orally (until end of month 2), to 2.5 mg/m²/day orally (until end of month 3) and to 1 mg/m²/day orally (until end of month 6). | Drug | With Intraoperative Steroids, Without Intraoperative Steroids |
Primary outcome
Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation
Time frame: 3 months after treatment
Graft loss is defined as being listed for a re-transplantation. The analysis was based on the locally performed biopsy assessments. Generally, patients not experiencing a relevant event (i.e., acute rejection, graft loss or death) were censored with the last visit date.
6 secondary outcomes
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three Months
Time frame: 3 months
Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six Months
Time frame: 3 and 6 months
Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation
Time frame: 3 months and 6 months
Number of Participants With Bacterial, Viral and Fungal Infections During Six Months
Time frame: 6 months
Time of Onset of a First Biopsy Proven Acute Rejection
Time frame: 6 months
Percentage of Participants With Treatment Failure Within Three and Six Months
Time frame: 3 and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2011.
- 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 study director
Novartis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Basiliximab, Cyclosporine/cyclosporine microemulsion and Steroid in people with Liver Transplantation and Infection, run by Novartis at 1 site in Germany.
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 2 inclusion and 15 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 22 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 22 Sep 2011). 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?
Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation (time frame: 3 months after treatment). 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 22 Sep 2011.