Evidence of Liver TransplantationPhase 3NCT00694408
A Pilot Trial of Pediatric Liver Transplantation Without Steroids
A Phase 3 study testing methyl prednisolone, hydrocortisone, prednisolone and No steroids in people with Evidence of Liver Transplantation, run by Birmingham Women's and Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Objective: The overall objective is to investigate whether a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation and whether it promotes tolerance. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Evidence of Liver Transplantation
- What is being tested?
- methyl prednisolone, hydrocortisone, prednisolone and No steroids
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2008to Aug 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children undergoing primary isolated hepatic transplantation.
- Age <=18 years
- Ability to provide informed consent
Who cannot join
- Children undergoing retransplantation.
- Transplantation for Intestinal failure associated liver disease.
- Multi-organ transplantation.
- Transplantation for autoimmune liver disease.
- Transplantation for extra hepatic malignancy.
- Pre-existing need for oral steroids, or high dose inhaled steroids sufficient to require a steroid warning card.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Birmingham Children's Hospital
Birmingham, West Midlands, B4 6NH
About this study
Official title: A Randomized Pilot Trial of a Steroid-free Immunosuppressant Regimen in Pediatric Liver Transplantation
Objective:
The overall objective is to investigate whether a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation and whether it promotes tolerance.
Read the detailed description
3.2 Research question
Is it possible to avoid the use of corticosteroids in pediatric liver transplantation?
3.3 Trial objectives
This will be a pilot study to
- investigate to what degree a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation ii) investigate the effect of a steroid free immunosuppressive regimen on lymphocyte function and donor-specific immune responsiveness following pediatric liver transplantation iii) investigate the effect of a steroid free immunosuppressive regimen on expression of tissue markers of tolerance following pediatric liver transplantation
It is hoped that this pilot study will be used to develop a definitive multicentre study of a steroid free regimen.
- Conditions
- Evidence of Liver Transplantation
- Being tested
- methyl prednisolone, hydrocortisone, prednisolone, No steroids
- Keywords
- End stage liver disease, Paediatric liver transplantation, Steroid free immunosuppression
- Medical subject headings
- End Stage Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methyl prednisolone, hydrocortisone, prednisoloneDrug
Also called Methylprednisolone;Hydrocortisone;Prednisolone
Will be specific dependant on weight of patients
No steroidsOther
Children undergoing primary liver transplant will receive monoclonal antibodies and tacrolimus as per protocol
| Study group | Role | What they receive |
|---|---|---|
| Steroid immunosuppressive regimen | Active comparator | Freedom from rejection and safety in children undergoing paediatric liver transplant using steroid containing immunosuppression regimen post transplant. This group of patients will receive steroids in conjunction with other prescribed immunosuppressive agents. Intervention is use of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management Receives: Drug: methyl prednisolone, hydrocortisone, prednisolone |
| Steroid free immunosuppressive regimen | Active comparator | Freedom from rejection and safety in children undergoing paediatric liver transplant using steroid free immunosuppression regimen post transplant. The patients in this arm will receive immunosuppression but not steroids to compare with those treated with steroids to measure differences in rejection and safety of a steroid free immunosuppressive regimen. Intervention is omission of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management. No steroids will be used routinely in this arm Receives: Other: No steroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint: The development of histologically proven acute rejection. (within 12 months
Measured: 12m
Secondary outcomes (1)
The development of steroid resistant acute rejection 12 months. The expression of tissue and circulating markers of immune tolerance in first year post transplant The incidence of infection in the first year post transplant
Measured: 12m
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionAug 2011
- Study completionAug 2011
Why it stopped: Study terminated due to withdrawal from market of Daclizumab
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Evidence of 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Birmingham Women's and Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Patrick McKiernan, MRCP FRCPCH, Principal investigator, Birmingham Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00694408
- Sponsor's protocol ID
- SFPT/OL
- Status last verified
- Jan 2017
- First submitted
- 6 Jun 2008
- Last updated
- 20 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O Jr. Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation. 2003 Nov 15;76(9):1331-9. doi: 10.1097/01.TP.0000092950.54184.67.
PubMed 14627912Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol. 2005 Mar;20(3):418-26. doi: 10.1007/s00467-004-1786-4. Epub 2005 Feb 3.
PubMed 15690189Leonard H, Hornung T, Parry G, Dark JH. Pediatric cardiac transplant: results using a steroid-free maintenance regimen. Pediatr Transplant. 2003 Feb;7(1):59-63. doi: 10.1034/j.1399-3046.2003.00014.x.
PubMed 12581330Walsh PT, Taylor DK, Turka LA. Tregs and transplantation tolerance. J Clin Invest. 2004 Nov;114(10):1398-403. doi: 10.1172/JCI23238.
PubMed 15545987Yoshizawa A, Ito A, Li Y, Koshiba T, Sakaguchi S, Wood KJ, Tanaka K. The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation. Transplant Proc. 2005 Jan-Feb;37(1):37-9. doi: 10.1016/j.transproceed.2004.12.259.
PubMed 15808539Hathaway M, Adams DH. Demonstration that donor-specific nonresponsiveness in human liver allograft recipients is both rare and transient. Transplantation. 2004 Apr 27;77(8):1246-52. doi: 10.1097/01.tp.0000121136.84965.35.
PubMed 15114093Arora-Gupta N, Davies P, McKiernan P, Kelly DA. The effect of long-term calcineurin inhibitor therapy on renal function in children after liver transplantation. Pediatr Transplant. 2004 Apr;8(2):145-50. doi: 10.1046/j.1399-3046.2003.00132.x.
PubMed 15049794Evans HM, McKiernan PJ, Kelly DA. Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation. Transplantation. 2005 Jun 15;79(11):1575-80. doi: 10.1097/01.tp.0000163504.29054.3f.
PubMed 15940048Kelly D, Jara P, Rodeck B, Lykavieris P, Burdelski M, Becker M, Gridelli B, Boillot O, Manzanares J, Reding R. Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial. Lancet. 2004 Sep 18-24;364(9439):1054-61. doi: 10.1016/S0140-6736(04)17060-8.
PubMed 15380964Reding R, Gras J, Sokal E, Otte JB, Davies HF. Steroid-free liver transplantation in children. Lancet. 2003 Dec 20;362(9401):2068-70. doi: 10.1016/S0140-6736(03)15104-5.
PubMed 14697809
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Pilot Trial of a Steroid-free Immunosuppressant Regimen in Pediatric Liver Transplantation
- ClinicalTrials.gov ID
- NCT00694408
- Acronym / sponsor ID
- SFPT/OL
- Conditions
- Evidence of Liver Transplantation
- Keywords
- End stage liver disease, Paediatric liver transplantation, Steroid free immunosuppression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to withdrawal from market of Daclizumab
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Birmingham Women's and Children's NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- Jun 2008
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 10 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objective:
The overall objective is to investigate whether a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation and whether it promotes tolerance.
Detailed description
3.2 Research question
Is it possible to avoid the use of corticosteroids in pediatric liver transplantation?
3.3 Trial objectives
This will be a pilot study to
- investigate to what degree a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation ii) investigate the effect of a steroid free immunosuppressive regimen on lymphocyte function and donor-specific immune responsiveness following pediatric liver transplantation iii) investigate the effect of a steroid free immunosuppressive regimen on expression of tissue markers of tolerance following pediatric liver transplantation
It is hoped that this pilot study will be used to develop a definitive multicentre study of a steroid free regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Steroid immunosuppressive regimen | Active comparator | Drug: methyl prednisolone, hydrocortisone, prednisoloneFreedom from rejection and safety in children undergoing paediatric liver transplant using steroid containing immunosuppression regimen post transplant. This group of patients will receive steroids in conjunction with other prescribed immunosuppressive agents. Intervention is use of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management |
| Steroid free immunosuppressive regimen | Active comparator | Other: No steroidsFreedom from rejection and safety in children undergoing paediatric liver transplant using steroid free immunosuppression regimen post transplant. The patients in this arm will receive immunosuppression but not steroids to compare with those treated with steroids to measure differences in rejection and safety of a steroid free immunosuppressive regimen. Intervention is omission of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management. No steroids will be used routinely in this arm |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Children undergoing primary isolated hepatic transplantation.
- Age <=18 years
- Ability to provide informed consent
Key exclusion criteria (6 listed)
- Children undergoing retransplantation.
- Transplantation for Intestinal failure associated liver disease.
- Multi-organ transplantation.
- Transplantation for autoimmune liver disease.
- Transplantation for extra hepatic malignancy.
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 |
|---|---|---|
| methyl prednisolone, hydrocortisone, prednisoloneAlso: Methylprednisolone;Hydrocortisone;PrednisoloneWill be specific dependant on weight of patients | Drug | Steroid immunosuppressive regimen |
| No steroidsChildren undergoing primary liver transplant will receive monoclonal antibodies and tacrolimus as per protocol | Other | Steroid free immunosuppressive regimen |
Primary outcome
Primary endpoint: The development of histologically proven acute rejection. (within 12 months
Time frame: 12m
1 secondary outcome
The development of steroid resistant acute rejection 12 months. The expression of tissue and circulating markers of immune tolerance in first year post transplant The incidence of infection in the first year post transplant
Time frame: 12m
Results and safety
The study was stopped early (reason given: Study terminated due to withdrawal from market of Daclizumab). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2017.
- Background: PubMed 14627912Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O Jr. Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation. 2003 Nov 15;76(9):1331-9. doi: 10.1097/01.TP.0000092950.54184.67.
- Background: PubMed 15690189Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol. 2005 Mar;20(3):418-26. doi: 10.1007/s00467-004-1786-4. Epub 2005 Feb 3.
- Background: PubMed 12581330Leonard H, Hornung T, Parry G, Dark JH. Pediatric cardiac transplant: results using a steroid-free maintenance regimen. Pediatr Transplant. 2003 Feb;7(1):59-63. doi: 10.1034/j.1399-3046.2003.00014.x.
- Background: PubMed 15545987Walsh PT, Taylor DK, Turka LA. Tregs and transplantation tolerance. J Clin Invest. 2004 Nov;114(10):1398-403. doi: 10.1172/JCI23238.
- Background: PubMed 15808539Yoshizawa A, Ito A, Li Y, Koshiba T, Sakaguchi S, Wood KJ, Tanaka K. The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation. Transplant Proc. 2005 Jan-Feb;37(1):37-9. doi: 10.1016/j.transproceed.2004.12.259.
- Background: PubMed 15114093Hathaway M, Adams DH. Demonstration that donor-specific nonresponsiveness in human liver allograft recipients is both rare and transient. Transplantation. 2004 Apr 27;77(8):1246-52. doi: 10.1097/01.tp.0000121136.84965.35.
- Background: PubMed 15049794Arora-Gupta N, Davies P, McKiernan P, Kelly DA. The effect of long-term calcineurin inhibitor therapy on renal function in children after liver transplantation. Pediatr Transplant. 2004 Apr;8(2):145-50. doi: 10.1046/j.1399-3046.2003.00132.x.
- Background: PubMed 15940048Evans HM, McKiernan PJ, Kelly DA. Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation. Transplantation. 2005 Jun 15;79(11):1575-80. doi: 10.1097/01.tp.0000163504.29054.3f.
- Background: PubMed 15380964Kelly D, Jara P, Rodeck B, Lykavieris P, Burdelski M, Becker M, Gridelli B, Boillot O, Manzanares J, Reding R. Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial. Lancet. 2004 Sep 18-24;364(9439):1054-61. doi: 10.1016/S0140-6736(04)17060-8.
- Background: PubMed 14697809Reding R, Gras J, Sokal E, Otte JB, Davies HF. Steroid-free liver transplantation in children. Lancet. 2003 Dec 20;362(9401):2068-70. doi: 10.1016/S0140-6736(03)15104-5.
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.
Patrick McKiernan, MRCP FRCPCH principal investigator
Birmingham Children's Hospital
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 methyl prednisolone, hydrocortisone, prednisolone and No steroids in people with Evidence of Liver Transplantation, run by Birmingham Women's and Children's NHS Foundation Trust at 1 site in United Kingdom.
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 6 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: stopped early, as of the sponsor's last update on 20 Jan 2017. 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 United Kingdom. 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?
The study was stopped early (reason given: Study terminated due to withdrawal from market of Daclizumab). Results are not available in the source record.
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?
Primary endpoint: The development of histologically proven acute rejection. (within 12 months (time frame: 12m). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00694408, which also lists 10 linked publications.
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 20 Jan 2017.