Acute Rejection of Renal TransplantPhase 4NCT00943228
Intensified Dosing of Cellcept (Mycophenolate Mofetil) in Kidney Transplantation
A Phase 4 study testing mycophenolate mofetil in people with Acute Rejection of Renal Transplant, run by Nova Scotia Health Authority at 1 site in Canada.
Trial summary
The primary objective of this study is to determine whether 4 grams daily of mycophenolate mofetil (MMF) results in a greater proportion of individuals adequately exposed as measured by drug levels (area under the curve of > 40 mg*hr/L). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Rejection of Renal Transplant
- What is being tested?
- mycophenolate mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2010to Feb 2012
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing single organ kidney transplantation.
- Age > 18 years old.
- Patients who would normally receive our standard therapy of basiliximab, tacrolimus, MMF and steroids.
- All patients will be required to sign informed consent.
Who cannot join
- Patients will be excluded if they require anti-thymocyte induction therapy, have documented gastroparesis, have known intolerance to MMF, or are prescribed cyclosporine.
- As a standard policy all women of childbearing age will be informed about the risks of all immunosuppressive drugs on fetal outcomes and will be required to use 2 forms of birth control.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intensified Dosing of Cellcept in Kidney Transplantation Trial
The primary objective of this study is to determine whether 4 grams daily of mycophenolate mofetil (MMF) results in a greater proportion of individuals adequately exposed as measured by drug levels (area under the curve of > 40 mg*hr/L).
Read the detailed description
Several studies have shown that early exposure to adequate levels of immunosuppression are required to reduce acute rejection rates in kidney transplantation.(1, 2) Our center has shown that early exposure of mycophenolate mofetil (MMF or Cellcept) is associated with acute rejection rates and that many patients are underexposed in the early transplant period.(2) In a recently completed multicenter Canadian (CLEAR) study we found that higher doses of mycophenolate mofetil (MMF 3 grams daily versus 2 grams daily) were associated with better early exposure by day 5 and that this was associated with less rejection but no increase in toxicity.(3) The best cut point that discriminated between low and high rejection rates was a mycophenolic acid (MPA) 12 hour area under the curve (AUC) of 40 mg*hr/L. Patients below this level experienced rejection rates of 50% compared to <16% for those above this level. Even with the higher dose 26% of subjects were inadequately exposed. Since medication adjustments based on drug levels is hampered by steady state conditions and the turn around time of MPA testing we are interested in exploring even higher initial doses of MMF with the aim to maximize the numbers of patients achieving adequate early exposure to MPA.
Objectives:
The primary objective of this study is to determine whether 4 gms daily of MMF results in a greater proportion of individuals adequately exposed as measured by a day 5 MPA AUC of >40 mg*hr/L.
The secondary objectives of this study are to assess the ability of this strategy to achieve target MPA AUC exposure of 40-60 mg*hr/L by day 14 and to determine the distribution of MMF doses that are necessary to achieve this level of exposure. Safety data (hemoglobin and WBC counts, need for further dose changes based on gastrointestinal intolerance, acute rejection, renal function, and wound infection) will be also collected over the first 3 months post transplantation.
- Conditions
- Acute Rejection of Renal Transplant
- Being tested
- mycophenolate mofetil
- Keywords
- Renal transplantation, Adequate exposure, Acute rejection, mycophenolate mofetil, immunosuppression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called MMF, Cellcept
High dose 4gms daily
| Study group | Role | What they receive |
|---|---|---|
| mycophenolate mofetil | Experimental | mycophenolate mofetil 2000mg BID (4g/day) for 14 days, followed by mycophenolate 1000mg BID (2g/day) thereafter Receives: Drug: mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adequate drug exposure. MPA AUC > 40 mg*hr/l
Measured: First two weeks - 14 days
Secondary outcomes (2)
Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea).
Measured: First two weeks - 14 days
Leukopenia, anemia, thrombocytopenia and infection.
Measured: First two weeks - 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2009 (estimated)
- Study startFeb 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Rejection of Renal TransplantStudies of the same condition, open and under way.
- More trials run by Nova Scotia Health AuthorityThe 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 4
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bryce A Kiberd, MD, Principal investigator, Dalhousie University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00943228
- Sponsor's protocol ID
- IDOC001
- Status last verified
- Aug 2012
- First submitted
- 6 Jul 2009
- Last updated
- 9 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Kiberd BA, Lawen J, Daley C. Limits to intensified mycophenolate mofetil dosing in kidney transplantation. Ther Drug Monit. 2012 Dec;34(6):736-8. doi: 10.1097/FTD.0b013e31826d7bfa.
PubMed 23007746
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intensified Dosing of Cellcept in Kidney Transplantation Trial
- ClinicalTrials.gov ID
- NCT00943228
- Acronym / sponsor ID
- IDOC001
- Conditions
- Acute Rejection of Renal Transplant
- Keywords
- Renal transplantation, Adequate exposure, Acute rejection, mycophenolate mofetil, immunosuppression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 22 Jul 2009 (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.
The primary objective of this study is to determine whether 4 grams daily of mycophenolate mofetil (MMF) results in a greater proportion of individuals adequately exposed as measured by drug levels (area under the curve of > 40 mg*hr/L).
Detailed description
Several studies have shown that early exposure to adequate levels of immunosuppression are required to reduce acute rejection rates in kidney transplantation.(1, 2) Our center has shown that early exposure of mycophenolate mofetil (MMF or Cellcept) is associated with acute rejection rates and that many patients are underexposed in the early transplant period.(2) In a recently completed multicenter Canadian (CLEAR) study we found that higher doses of mycophenolate mofetil (MMF 3 grams daily versus 2 grams daily) were associated with better early exposure by day 5 and that this was associated with less rejection but no increase in toxicity.(3) The best cut point that discriminated between low and high rejection rates was a mycophenolic acid (MPA) 12 hour area under the curve (AUC) of 40 mg*hr/L. Patients below this level experienced rejection rates of 50% compared to <16% for those above this level. Even with the higher dose 26% of subjects were inadequately exposed. Since medication adjustments based on drug levels is hampered by steady state conditions and the turn around time of MPA testing we are interested in exploring even higher initial doses of MMF with the aim to maximize the numbers of patients achieving adequate early exposure to MPA.
Objectives:
The primary objective of this study is to determine whether 4 gms daily of MMF results in a greater proportion of individuals adequately exposed as measured by a day 5 MPA AUC of >40 mg*hr/L.
The secondary objectives of this study are to assess the ability of this strategy to achieve target MPA AUC exposure of 40-60 mg*hr/L by day 14 and to determine the distribution of MMF doses that are necessary to achieve this level of exposure. Safety data (hemoglobin and WBC counts, need for further dose changes based on gastrointestinal intolerance, acute rejection, renal function, and wound infection) will be also collected over the first 3 months post transplantation.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mycophenolate mofetil | Experimental | Drug: mycophenolate mofetilmycophenolate mofetil 2000mg BID (4g/day) for 14 days, followed by mycophenolate 1000mg BID (2g/day) thereafter |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients undergoing single organ kidney transplantation.
- Age > 18 years old.
- Patients who would normally receive our standard therapy of basiliximab, tacrolimus, MMF and steroids.
- All patients will be required to sign informed consent.
Key exclusion criteria (2 listed)
- Patients will be excluded if they require anti-thymocyte induction therapy, have documented gastroparesis, have known intolerance to MMF, or are prescribed cyclosporine.
- As a standard policy all women of childbearing age will be informed about the risks of all immunosuppressive drugs on fetal outcomes and will be required to use 2 forms of birth control.
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 |
|---|---|---|
| mycophenolate mofetilAlso: MMF, CellceptHigh dose 4gms daily | Drug | mycophenolate mofetil |
Primary outcome
Adequate drug exposure. MPA AUC > 40 mg*hr/l
Time frame: First two weeks - 14 days
2 secondary outcomes
Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea).
Time frame: First two weeks - 14 days
Leukopenia, anemia, thrombocytopenia and infection.
Time frame: First two weeks - 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2012.
- Derived from this study: PubMed 23007746Kiberd BA, Lawen J, Daley C. Limits to intensified mycophenolate mofetil dosing in kidney transplantation. Ther Drug Monit. 2012 Dec;34(6):736-8. doi: 10.1097/FTD.0b013e31826d7bfa.
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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.
Bryce A Kiberd, MD principal investigator
Dalhousie University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing mycophenolate mofetil in people with Acute Rejection of Renal Transplant, run by Nova Scotia Health Authority at 1 site in Canada.
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 4 inclusion and 2 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 9 Aug 2012. 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 Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adequate drug exposure. MPA AUC > 40 mg*hr/l (time frame: First two weeks - 14 days). 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 NCT00943228, which also lists 1 linked publication.
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 9 Aug 2012.