Wegener's GranulomatosisPhase 2/3MEPEXNCT01408836
Plasma Exchange for Renal Vasculitis
A Phase 2/3 study testing Plasma exchange, Intravenous methyl prednisolone and Methyl prednisolone in people with Wegener's Granulomatosis and Microscopic Polyangiitis, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The purpose of this study is to test whether additional therapy with plasma exchange improves the chances of kidney recovery in severe kidney vasculitis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Wegener's Granulomatosis, Microscopic Polyangiitis
- What is being tested?
- Plasma exchange, Intravenous methyl prednisolone and Methyl prednisolone
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 1995to Dec 2003
- Phase
- Phase 2/3
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Wegener's granulomatosis or microscopic polyangiitis, using criteria adapted by EUVAS from the disease definitions of the Chapel Hill consensus conference
- Biopsy proven, pauci-immune, necrotising and/or crescentic glomerulonephritis, in the absence of other defined glomerulopathy
- Severe renal impairment defined by: (i) oliguria (<400ml/24hr), or (ii) intention to commence dialysis within 48 hours of admission, and (iii) creatinine >500umol/l (5.8mg/dl).
Who cannot join
- Age under 18 or over 80 years
- Inadequate contraception in women of child-bearing age
- Pregnancy
- Previous malignancy
- Hepatitis B antigenaemia, anti-hepatitis C virus or anti-human immunodeficiency virus antibody
- Diagnosis of Churg-Strauss syndrome, Henoch-Schönlein purpura, rheumatoid vasculitis, mixed essential cryoglobulinaemia or systemic lupus erythematosus
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- Circulating anti-GBM antibodies or linear IgG staining of the GBM on renal biopsy
- Life-threatening non-renal manifestations of vasculitis, including alveolar hemorrhage requiring mechanical ventilation within 24 hours of admission
- On dialysis for > two weeks prior to entry
- Creatinine > 200umol/l (2.3mg/dl) one year or more before entry
- A second clearly defined cause of renal failure
- Previous episode of biopsy-proven necrotising and/or crescentic glomerulonephritis
- > two weeks treatment with cyclophosphamide or azathioprine
- > 500mg IV methyl prednisolone
- Plasma exchange within the preceding year
- > three months treatment with oral prednisolone
- Allergy to study medications.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Addenbrooke's Hospital
Cambridge, Cambridge, CB22QQ
About this study
Official title: Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis
The purpose of this study is to test whether additional therapy with plasma exchange improves the chances of kidney recovery in severe kidney vasculitis.
Read the detailed description
Primary systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA), is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation often progresses to end stage renal disease despite immunosuppressive therapy. We investigated whether the addition of plasma exchange was more effective than intravenous (IV) methyl prednisolone in the achievement of renal recovery for ANCA associated systemic vasculitis presenting with a serum creatinine above 500umol/l (5.8mg/dl).
137 patients with a new diagnosis of ANCA associated systemic vasculitis, serum creatinine above 500umol/l (5.8mg/dl) and a renal biopsy demonstrating a focal, necrotizing glomerulonephritis were randomized to receive seven plasma exchanges or IV methyl prednisolone 1000mg/day for three days. Both groups were treated with cyclophosphamide and oral prednisolone. The primary end-point was dialysis independence with a serum creatinine below 500umol/l (5.8mg/dl) at three months. Secondary end-points included renal and patient survival at 12 months and severe adverse event rates.
- Conditions
- Wegener's Granulomatosis, Microscopic Polyangiitis
- Being tested
- Plasma exchange, Intravenous methyl prednisolone, Methyl prednisolone
- Keywords
- Vasculitis, ANCA, Therapy, Plasma exchange, Immunosuppression
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma exchangeProcedure or surgery
Plasma exchange
Intravenous methyl prednisoloneDrug
Intravenous methyl prednisolone
Methyl prednisoloneDrug
methyl prednisolone
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Plasma exchange x 7 over 14 days Receives: Procedure: Plasma exchange |
| 2 | Active comparator | Methyl prednisolone 1g x 3 Receives: Drug: Intravenous methyl prednisolone; Drug: Methyl prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal recovery
Measured: Three months
Secondary outcomes (3)
End stage renal disease at 12 months
Measured: 12 months
Serum creatinine at 12 months
Measured: 12 months
Severe adverse events
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2011 (estimated)
- Study startMar 1995
- Primary completionJun 2003
- Study completionDec 2003
Why it stopped: Completed
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 Wegener's GranulomatosisStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Birmingham, Imperial College London, London North West Healthcare NHS Trust, University Hospitals, Leicester, Lund University Hospital, University Medical Center Groningen, Fundacio Clinic Barcelona, University of Helsinki
- Investigators
- Niels Rasmussen, MD, Study director, Righospitalet, Copenhagen, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01408836
- Sponsor's protocol ID
- BMH4-CT97-2328
- Acronym
- MEPEX
- Status last verified
- Jul 2011
- First submitted
- 2 Aug 2011
- Last updated
- 3 Aug 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Walsh M, Casian A, Flossmann O, Westman K, Hoglund P, Pusey C, Jayne DR; European Vasculitis Study Group (EUVAS). Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 2013 Aug;84(2):397-402. doi: 10.1038/ki.2013.131. Epub 2013 Apr 24.
PubMed 23615499
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis
- ClinicalTrials.gov ID
- NCT01408836
- Acronym / sponsor ID
- MEPEX / BMH4-CT97-2328
- Conditions
- Wegener's Granulomatosis, Microscopic Polyangiitis
- Keywords
- Vasculitis, ANCA, Therapy, Plasma exchange, Immunosuppression
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University Hospital Birmingham, Imperial College London, London North West Healthcare NHS Trust, University Hospitals, Leicester, Lund University Hospital, University Medical Center Groningen, Fundacio Clinic Barcelona, University of Helsinki
- Study start
- Mar 1995
- Primary completion
- Jun 2003 (actual)
- Study completion
- Dec 2003 (actual)
- First posted
- 3 Aug 2011 (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 purpose of this study is to test whether additional therapy with plasma exchange improves the chances of kidney recovery in severe kidney vasculitis.
Detailed description
Primary systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA), is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation often progresses to end stage renal disease despite immunosuppressive therapy. We investigated whether the addition of plasma exchange was more effective than intravenous (IV) methyl prednisolone in the achievement of renal recovery for ANCA associated systemic vasculitis presenting with a serum creatinine above 500umol/l (5.8mg/dl).
137 patients with a new diagnosis of ANCA associated systemic vasculitis, serum creatinine above 500umol/l (5.8mg/dl) and a renal biopsy demonstrating a focal, necrotizing glomerulonephritis were randomized to receive seven plasma exchanges or IV methyl prednisolone 1000mg/day for three days. Both groups were treated with cyclophosphamide and oral prednisolone. The primary end-point was dialysis independence with a serum creatinine below 500umol/l (5.8mg/dl) at three months. Secondary end-points included renal and patient survival at 12 months and severe adverse event rates.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Plasma exchangePlasma exchange x 7 over 14 days |
| 2 | Active comparator | Drug: Intravenous methyl prednisolone, Drug: Methyl prednisoloneMethyl prednisolone 1g x 3 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Wegener's granulomatosis or microscopic polyangiitis, using criteria adapted by EUVAS from the disease definitions of the Chapel Hill consensus conference
- Biopsy proven, pauci-immune, necrotising and/or crescentic glomerulonephritis, in the absence of other defined glomerulopathy
- Severe renal impairment defined by: (i) oliguria (<400ml/24hr), or (ii) intention to commence dialysis within 48 hours of admission, and (iii) creatinine >500umol/l (5.8mg/dl).
Key exclusion criteria (17 listed)
- Age under 18 or over 80 years
- Inadequate contraception in women of child-bearing age
- Pregnancy
- Previous malignancy
- Hepatitis B antigenaemia, anti-hepatitis C virus or anti-human immunodeficiency virus antibody
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 |
|---|---|---|
| Plasma exchangePlasma exchange | Procedure or surgery | 1 |
| Intravenous methyl prednisoloneIntravenous methyl prednisolone | Drug | 2 |
| Methyl prednisolonemethyl prednisolone | Drug | 2 |
Primary outcome
Renal recovery
Time frame: Three months
3 secondary outcomes
End stage renal disease at 12 months
Time frame: 12 months
Serum creatinine at 12 months
Time frame: 12 months
Severe adverse events
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Completed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2011.
- Derived from this study: PubMed 23615499Walsh M, Casian A, Flossmann O, Westman K, Hoglund P, Pusey C, Jayne DR; European Vasculitis Study Group (EUVAS). Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 2013 Aug;84(2):397-402. doi: 10.1038/ki.2013.131. Epub 2013 Apr 24.
- EUVAS homepageLink provided by the sponsor.
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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.
Niels Rasmussen, MD study director
Righospitalet, Copenhagen, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Plasma exchange, Intravenous methyl prednisolone and Methyl prednisolone in people with Wegener's Granulomatosis and Microscopic Polyangiitis, run by Cambridge University Hospitals 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 17 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 3 Aug 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 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: Completed). 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?
Renal recovery (time frame: Three months). 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 NCT01408836, 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 3 Aug 2011.