Myasthenia GravisPhase 4MYACORNCT00987116
Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis
A Phase 4 study testing Prednisone - Azathioprine in people with Myasthenia Gravis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Pathology - Generalized myasthenia gravis (MG) is cause of muscle weakness that can have a significant impact on daily life activity but can also be, when respiratory or bulbar muscles are involved, life-threatening. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- Prednisone - Azathioprine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2009to Sep 2017
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written consent of the patient, after informing
- Generalized MG of grade III, IV or V - Classification MGFA
- Follow-up on 15 months possible and accepted by patients
Who cannot join
- Age<18 or >80 years
- Pregnancy
- Myasthenia of grade I or II of MGFA
- Patients already treated with prednisone or azathioprine
- Contraindication for prednisone or azathioprine
- Other associated disease requiring a treatment with prednisone or azathioprine
- Weight >100kg
- Invasive thymoma
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Two Tapering Strategies of Prednisone in Patients With Generalised Myasthenia Gravis Treated With Prednisone and Azathioprine: a Single-blind Randomised Controlled Multicenter Study
Pathology - Generalized myasthenia gravis (MG) is cause of muscle weakness that can have a significant impact on daily life activity but can also be, when respiratory or bulbar muscles are involved, life-threatening.
Rationale - Additionally to thymectomy, which indication of is still debated in absence of thymoma, the long-term treatment of generalized myasthenia gravis includes usually prednisone and azathioprine. However, the most used scheme for prescribing and tapering corticosteroid in MG resulted in a very important cumulative dose of prednisone. Indeed, at twelve month, more than 50 percent of patients are still daily treated with at least 18 mg of prednisone and the proportion of patients who are in remission and no longer taking prednisone is very low (Palace and NEWSOM Davis, Neurology 1998). Prolonged corticosteroid therapy is accompanied with various and major side effects, hypertension, osteoporosis, weight gain, glaucoma. Therefore, tapering, eventually discontinuing, prednisone earlier is a relevant therapeutic goal.
Read more
For this reason, the investigators will compare to the standard one, a strategy consisting of a rapid decrease in corticosteroid.
Objective - To assess whether, in patients with generalized MG requiring a long-term treatment with corticosteroids and azathioprine, that the strategy of rapid tapering allows discontinuing more rapidly the prednisone for equivalent efficacy than the classical strategy.
Read the detailed description
Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.
Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.
Duration of follow-up is 15 months.
In both arms, Myasthenia Muscular Score (MMS), activities of Daily Living Scale (ADLS), MGFA Clinical Classification and MGFA Post-Intervention Status as well as prednisone and azathioprine side effects will be monthly assessed by a senior neurologist who will be blind for treatment group. A second physician, who is aware of the patient's therapeutic group, will then prescribe prednisone dose and tapering for a month, according to MGFA Post-Intervention Status.
In case of worsening, prednisone dose will be increased. In case of exacerbation, the patients will be hospitalised for eventually IvIg infusion or plasma exchange. In case of a severe side effect, prednisone will be reduced irrespectively of MGFA Post-Intervention Status. In case of side effect, azathioprine will be replaced by mycophenolate mofetil.
- Conditions
- Myasthenia Gravis
- Being tested
- Prednisone - Azathioprine
- Keywords
- Myasthenia gravis, Steroids side effects, Comparison of strategies for tapering steroids, Generalized MG corresponding to grade III, IV or V of MGFA
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prednisone - AzathioprineDrug
Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.
Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.
| Study group | Role | What they receive |
|---|---|---|
| Starting dose Prednisone Azathioprine | Active comparator | Classical Strategy Receives: Drug: Prednisone - Azathioprine |
| Starting dose Prednisone - Azathioprine | Active comparator | Rapid strategy Receives: Drug: Prednisone - Azathioprine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who have reach minimal manifestation state (according to MGFA criteria) and are not treated with prednisone after 12 months of treatment and have not relapsed during the next 3 months.
Measured: 15 months
Secondary outcomes (7)
Cumulative dose of prednisone at twelve months
Measured: 15 MONTHS
Proportion of patients having reached minimal manifestation state 12 months
Measured: 15 MONTHS
Time for reaching the improvement or minimal manifestation state (MGFA criteria)
Measured: 15 MONTHS
Frequency of exacerbations within the first 15 months after randomization
Measured: 15 MONTHS
Frequency of treatment by IvIg or plasma exchange within the first 15 months after randomization
Measured: 15 MONTHS
Frequency and type of complications related to prednisone.
Measured: 15 MONTHS
Frequency and type of complications of azathioprine
Measured: 15 MONTHS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2009 (estimated)
- Study startJun 2009
- Primary completionJul 2017
- Study completionSep 2017
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 Myasthenia GravisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tarek Sharshar, MD PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987116
- Sponsor's protocol ID
- P051055
- Acronym
- MYACOR
- Status last verified
- Oct 2017
- First submitted
- 29 Sep 2009
- Last updated
- 13 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sharshar T, Porcher R, Demeret S, Tranchant C, Gueguen A, Eymard B, Nadaj-Pakleza A, Spinazzi M, Grimaldi L, Birnbaum S, Friedman D, Clair B; MYACOR Study Group. Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial. JAMA Neurol. 2021 Apr 1;78(4):426-433. doi: 10.1001/jamaneurol.2020.5407.
PubMed 33555314
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Two Tapering Strategies of Prednisone in Patients With Generalised Myasthenia Gravis Treated With Prednisone and Azathioprine: a Single-blind Randomised Controlled Multicenter Study
- ClinicalTrials.gov ID
- NCT00987116
- Acronym / sponsor ID
- MYACOR / P051055
- Conditions
- Myasthenia Gravis
- Keywords
- Myasthenia gravis, Steroids side effects, Comparison of strategies for tapering steroids, Generalized MG corresponding to grade III, IV or V of MGFA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2009 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 30 Sep 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.
Pathology - Generalized myasthenia gravis (MG) is cause of muscle weakness that can have a significant impact on daily life activity but can also be, when respiratory or bulbar muscles are involved, life-threatening.
Rationale - Additionally to thymectomy, which indication of is still debated in absence of thymoma, the long-term treatment of generalized myasthenia gravis includes usually prednisone and azathioprine. However, the most used scheme for prescribing and tapering corticosteroid in MG resulted in a very important cumulative dose of prednisone. Indeed, at twelve month, more than 50 percent of patients are still daily treated with at least 18 mg of prednisone and the proportion of patients who are in remission and no longer taking prednisone is very low (Palace and NEWSOM Davis, Neurology 1998). Prolonged corticosteroid therapy is accompanied with various and major side effects, hypertension, osteoporosis, weight gain, glaucoma. Therefore, tapering, eventually discontinuing, prednisone earlier is a relevant therapeutic goal.
For this reason, the investigators will compare to the standard one, a strategy consisting of a rapid decrease in corticosteroid.
Objective - To assess whether, in patients with generalized MG requiring a long-term treatment with corticosteroids and azathioprine, that the strategy of rapid tapering allows discontinuing more rapidly the prednisone for equivalent efficacy than the classical strategy.
Detailed description
Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.
Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.
Duration of follow-up is 15 months.
In both arms, Myasthenia Muscular Score (MMS), activities of Daily Living Scale (ADLS), MGFA Clinical Classification and MGFA Post-Intervention Status as well as prednisone and azathioprine side effects will be monthly assessed by a senior neurologist who will be blind for treatment group. A second physician, who is aware of the patient's therapeutic group, will then prescribe prednisone dose and tapering for a month, according to MGFA Post-Intervention Status.
In case of worsening, prednisone dose will be increased. In case of exacerbation, the patients will be hospitalised for eventually IvIg infusion or plasma exchange. In case of a severe side effect, prednisone will be reduced irrespectively of MGFA Post-Intervention Status. In case of side effect, azathioprine will be replaced by mycophenolate mofetil.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Starting dose Prednisone Azathioprine | Active comparator | Drug: Prednisone - AzathioprineClassical Strategy |
| Starting dose Prednisone - Azathioprine | Active comparator | Drug: Prednisone - AzathioprineRapid strategy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Written consent of the patient, after informing
- Generalized MG of grade III, IV or V - Classification MGFA
- Follow-up on 15 months possible and accepted by patients
Key exclusion criteria (8 listed)
- Age<18 or >80 years
- Pregnancy
- Myasthenia of grade I or II of MGFA
- Patients already treated with prednisone or azathioprine
- Contraindication for prednisone or azathioprine
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 |
|---|---|---|
| Prednisone - AzathioprineRapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day. Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days. | Drug | Starting dose Prednisone - Azathioprine, Starting dose Prednisone Azathioprine |
Primary outcome
Proportion of patients who have reach minimal manifestation state (according to MGFA criteria) and are not treated with prednisone after 12 months of treatment and have not relapsed during the next 3 months.
Time frame: 15 months
7 secondary outcomes
Cumulative dose of prednisone at twelve months
Time frame: 15 MONTHS
Proportion of patients having reached minimal manifestation state 12 months
Time frame: 15 MONTHS
Time for reaching the improvement or minimal manifestation state (MGFA criteria)
Time frame: 15 MONTHS
Frequency of exacerbations within the first 15 months after randomization
Time frame: 15 MONTHS
Frequency of treatment by IvIg or plasma exchange within the first 15 months after randomization
Time frame: 15 MONTHS
Frequency and type of complications related to prednisone.
Time frame: 15 MONTHS
Frequency and type of complications of azathioprine
Time frame: 15 MONTHS
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 13 Oct 2017.
- Derived from this study: PubMed 33555314Sharshar T, Porcher R, Demeret S, Tranchant C, Gueguen A, Eymard B, Nadaj-Pakleza A, Spinazzi M, Grimaldi L, Birnbaum S, Friedman D, Clair B; MYACOR Study Group. Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial. JAMA Neurol. 2021 Apr 1;78(4):426-433. doi: 10.1001/jamaneurol.2020.5407.
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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.
Tarek Sharshar, MD PH principal investigator
Assistance Publique - Hôpitaux de Paris
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 Prednisone - Azathioprine in people with Myasthenia Gravis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 8 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 13 Oct 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 France. 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?
Proportion of patients who have reach minimal manifestation state (according to MGFA criteria) and are not treated with prednisone after 12 months of treatment and have not relapsed during the next 3 months. (time frame: 15 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 NCT00987116, 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 13 Oct 2017.