Glomerulonephritis, MembranousPhase 4MTACNCT00843856
Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis
A Phase 4 study testing tacrolimus and tacrolimus and mycophenolate mofetil in people with Glomerulonephritis, Membranous, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
Study Hypothesis: When mycophenolate mofetil is added to tacrolimus in the treatment of membranous glomerulonephritis it is likely to improve the initial response to treatment and reduce the risk of relapse on stopping therapy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Glomerulonephritis, Membranous
- What is being tested?
- tacrolimus and tacrolimus and mycophenolate mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Mar 2009to 18 Sep 2018
- Phase
- Phase 4
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Idiopathic membranous glomerulonephritis on renal biopsy
- Proteinuria - protein/creatinine ratio (PCR) > 100 units with hypoalbuminaemia or PCR > 300 units with normal serum albumin despite 3 months treatment with maximum tolerated doses of ace inhibitors and angiotensin 2 antagonists (or shorter if life threatening complications of nephrotic syndrome require institution of immediate immunosuppression)
- Male or female patients aged 18 to 80 years
Who cannot join
- Hepatitis B hepatitis C or HIV positive
- Malignancy (all patients must have a CT chest abdomen and pelvis and other investigations if clinically indicated)
- Untreated infection
- Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception
- Any condition judged by the investigator that would cause the study to be detrimental to the patient
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mycophenolate Mofetil and Tacrolimus vs Tacrolimus Alone for the Treatment of Idiopathic Membranous Glomerulonephritis (IMG)
Study Hypothesis: When mycophenolate mofetil is added to tacrolimus in the treatment of membranous glomerulonephritis it is likely to improve the initial response to treatment and reduce the risk of relapse on stopping therapy.
Read the detailed description
Membranous nephropathy is a common cause of nephrotic syndrome in adults. It is difficult to treat and if persistent leads to end stage renal failure in a significant number of patients. It is currently treated in this institution with tacrolimus monotherapy. This is effective in the majority of patients in reducing proteinuria but the remissions are often partial and patients tend to relapse when the tacrolimus treatment is stopped. We propose to use mycophenolate mofetil in combination with tacrolimus with the aim of obtaining a more complete initial response to treatment, a decreased rate of relapse on withdrawal of therapy and less progression of renal failure. This will be a randomised control trial, patients will be randomised to receive treatment with tacrolimus alone (our current standard therapy)or treatment with tacrolimus and mycophenolate mofetil. Participants will receive treatment for up to 2 years and then be monitored for relapse of their nephrotic syndrome.
- Conditions
- Glomerulonephritis, Membranous
- Being tested
- tacrolimus, tacrolimus and mycophenolate mofetil
- Keywords
- Glomerulonephritis
- Medical subject headings
- Glomerulonephritis, Membranous, Glomerulonephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tacrolimusDrug
Also called prograff
tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml
tacrolimus and mycophenolate mofetilDrug
Also called prograf, cellcept
tacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenolate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L
| Study group | Role | What they receive |
|---|---|---|
| tacrolimus | Active comparator | Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L Receives: Drug: tacrolimus |
| tacrolimus and mycophenolate mofetil | Active comparator | tacrolimus 2mgs bd (adjusted to obtain levels 5-12mg/L and mycophenolate mofetil 500mg bd adjusted to obtain levels 1.5-3mg/L Receives: Drug: tacrolimus and mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patient Who Gained Remission From the Nephrotic Syndrome
Efficacy of mycophenolate in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy.
Measured: 10-109 weeks
Secondary outcomes (1)
Number of Patients Achieved Remission
The degree of remission of proteinuria obtained (complete or partial) The rate of decline of renal function measured by the Modification of Diet in Renal Disease equation for glomerular filtration rate.
Measured: 6-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study start3 Mar 2009
- Primary completionMar 2018
- Study completion18 Sep 2018
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Glomerulonephritis, MembranousStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Megan Griffith, MBChB PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00843856
- Sponsor's protocol ID
- 13HH1282
- Other IDs
- 2008-001009-41, 2008
- Acronym
- MTAC
- Status last verified
- Nov 2019
- First submitted
- 12 Feb 2009
- Last updated
- 12 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nikolopoulou A, Condon M, Turner-Stokes T, Cook HT, Duncan N, Galliford JW, Levy JB, Lightstone L, Pusey CD, Roufosse C, Cairns TD, Griffith ME. Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial. BMC Nephrol. 2019 Sep 6;20(1):352. doi: 10.1186/s12882-019-1539-z.
PubMed 31492152von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
PubMed 34778952
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mycophenolate Mofetil and Tacrolimus vs Tacrolimus Alone for the Treatment of Idiopathic Membranous Glomerulonephritis (IMG)
- ClinicalTrials.gov ID
- NCT00843856
- Acronym / sponsor ID
- MTAC / 13HH1282
- Conditions
- Glomerulonephritis, Membranous
- Keywords
- Glomerulonephritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Imperial College Healthcare NHS TrustUniversity, hospital or other
- Study start
- 3 Mar 2009 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- 18 Sep 2018 (actual)
- First posted
- 13 Feb 2009 (estimated)
- Results
- Posted 12 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Hypothesis: When mycophenolate mofetil is added to tacrolimus in the treatment of membranous glomerulonephritis it is likely to improve the initial response to treatment and reduce the risk of relapse on stopping therapy.
Detailed description
Membranous nephropathy is a common cause of nephrotic syndrome in adults. It is difficult to treat and if persistent leads to end stage renal failure in a significant number of patients. It is currently treated in this institution with tacrolimus monotherapy. This is effective in the majority of patients in reducing proteinuria but the remissions are often partial and patients tend to relapse when the tacrolimus treatment is stopped. We propose to use mycophenolate mofetil in combination with tacrolimus with the aim of obtaining a more complete initial response to treatment, a decreased rate of relapse on withdrawal of therapy and less progression of renal failure. This will be a randomised control trial, patients will be randomised to receive treatment with tacrolimus alone (our current standard therapy)or treatment with tacrolimus and mycophenolate mofetil. Participants will receive treatment for up to 2 years and then be monitored for relapse of their nephrotic syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tacrolimus | Active comparator | Drug: tacrolimusIntervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L |
| tacrolimus and mycophenolate mofetil | Active comparator | Drug: tacrolimus and mycophenolate mofetiltacrolimus 2mgs bd (adjusted to obtain levels 5-12mg/L and mycophenolate mofetil 500mg bd adjusted to obtain levels 1.5-3mg/L |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Idiopathic membranous glomerulonephritis on renal biopsy
- Proteinuria - protein/creatinine ratio (PCR) > 100 units with hypoalbuminaemia or PCR > 300 units with normal serum albumin despite 3 months treatment with maximum tolerated doses of ace inhibitors and angiotensin 2 antagonists (or shorter if life threatening complications of nephrotic syndrome require institution of immediate immunosuppression)
- Male or female patients aged 18 to 80 years
Key exclusion criteria (5 listed)
- Hepatitis B hepatitis C or HIV positive
- Malignancy (all patients must have a CT chest abdomen and pelvis and other investigations if clinically indicated)
- Untreated infection
- Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception
- Any condition judged by the investigator that would cause the study to be detrimental to the patient
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 |
|---|---|---|
| tacrolimusAlso: prografftacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml | Drug | tacrolimus |
| tacrolimus and mycophenolate mofetilAlso: prograf, cellcepttacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenolate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L | Drug | tacrolimus and mycophenolate mofetil |
Primary outcome
Number of Patient Who Gained Remission From the Nephrotic Syndrome
Time frame: 10-109 weeks
Efficacy of mycophenolate in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy.
1 secondary outcome
Number of Patients Achieved Remission
Time frame: 6-12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31492152Nikolopoulou A, Condon M, Turner-Stokes T, Cook HT, Duncan N, Galliford JW, Levy JB, Lightstone L, Pusey CD, Roufosse C, Cairns TD, Griffith ME. Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial. BMC Nephrol. 2019 Sep 6;20(1):352. doi: 10.1186/s12882-019-1539-z.
- Derived from this study: PubMed 34778952von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
- Individual participant dataSharing planned: No
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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.
Megan Griffith, MBChB PhD principal investigator
Imperial College London
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 tacrolimus and tacrolimus and mycophenolate mofetil in people with Glomerulonephritis, Membranous, run by Imperial College Healthcare NHS 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 5 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 12 Dec 2019. 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 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?
Yes. Results are posted in the registry (first posted 12 Dec 2019). 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 Patient Who Gained Remission From the Nephrotic Syndrome (time frame: 10-109 weeks). 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 NCT00843856, which also lists 2 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 12 Dec 2019.