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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06120673
Registration number
NCT06120673
Ethics application status
Date submitted
12/12/2022
Date registered
7/11/2023
Titles & IDs
Public title
REmission in Membranous Nephropathy International Trial (REMIT)
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Scientific title
International, Multi-centre Randomised Clinical Trial of Obinutuzumab Versus Corticosteroid and Cyclophosphamide in Primary Membranous Nephropathy (REMIT Trial).
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Secondary ID [1]
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AKTN 18.03
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Universal Trial Number (UTN)
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Trial acronym
REMIT
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Primary Membranous Nephropathy
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Condition category
Condition code
Renal and Urogenital
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Kidney disease
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Inflammatory and Immune System
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Autoimmune diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Oral prednisolone and cyclophosphamide
Experimental: Obinutuzumab -
Active comparator: Oral prednisolone and cyclophosphamide -
Treatment: Drugs: Obinutuzumab
Participants will receive an intravenous infusion of 1,000mg Obinutuzumab at Weeks 0, 2, 24 and 26.
Prior to the administration of obinutuzumab, the participant will receive pre-medications consisting of all three:
* IV methylprednisolone 80 mg,
* Paracetamol 1,000 mg orally,
* Either cetirizine 10 mg orally or diphenhydramine 50 mg orally. These pre-medications must be completed between 30 to 60 minutes prior to the obinutuzumab infusion.
Treatment: Drugs: Oral prednisolone and cyclophosphamide
Participants will receive a combination of oral prednisolone and cyclophosphamide with 2 options (Option A and B).
Option A: Cyclical prednisolone and cyclophosphamide with IV methylprednisolone
* IV methylprednisolone 500-1000 mg will be given on days 1, 2 and 3 at the start of months 1, 3, and 5.
* Oral prednisolone will be given at 0.5 mg/kg/day (max 50 mg/day) in months 1, 3, and 5.
* Oral cyclophosphamide will be given in months 2, 4 and 6, adjusted by age and weight
Option B: Concurrent prednisolone and cyclophosphamide without IV methylprednisolone
* Oral prednisolone will be given to meet a cumulative dose equivalent to 0.5 mg/kg/day for 90 days (max 50 mg/day).
* Oral cyclophosphamide will be given for 90 days, adjusted by age and weight
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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A ranked composite measure based efficacy, safety and quality of life at 24 months
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Assessment method [1]
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A ranked composite measure comprising of:
1. Efficacy (complete/partial remission) plus safety (type of adverse event) at 24 months
2. Number of adverse events up to 24 months
3. Quality of Life (EQ-5D) averaged over 24 months
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Timepoint [1]
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24 months
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Secondary outcome [1]
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Number of participants in Complete Remission (CR)
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Assessment method [1]
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Number of participants who have proteinuria of =3.0 g/day
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Timepoint [1]
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At 6, 12, 18, 24 month
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Secondary outcome [2]
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Number of participants in Partial Remission (PR)
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Assessment method [2]
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Number of participants who have proteinuria of between \>3.0 and 3.5 g/day and \>50% reduction from baseline proteinuria
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Timepoint [2]
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At 6, 12, 18, 24 month
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Secondary outcome [3]
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Number of participants in CR and/or PR
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Assessment method [3]
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Number of participants who meet complete and/or partial PMN remission definition
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Timepoint [3]
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At 6, 12, 18, 24 month
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Secondary outcome [4]
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Number of non-serious adverse events of special interest
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Assessment method [4]
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Number of protocol defined non-serious events of special interest (related to PMN or the study interventions)
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Timepoint [4]
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Up until 24 months
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Secondary outcome [5]
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Number of serious adverse events
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Assessment method [5]
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Number of protocol defined serious adverse events
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Timepoint [5]
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Up until 24 months
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Secondary outcome [6]
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Number of participants with a lack of response to PMN treatment
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Assessment method [6]
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Number of participants who have \<50% reduction in proteinuria from baseline or worsening (increasing in value from baseline) proteinuria, and had not achieved either PR or CR
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Timepoint [6]
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Up until 24 months
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Secondary outcome [7]
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Number of participants who relapse after CR or PR
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Assessment method [7]
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Number of participant who have a reappearance of proteinuria to \>3.5 g/day at a =50% higher level than the lowest post-treatment value in participants who had previously achieved either PR or CR
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Timepoint [7]
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Up until 24 months
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Secondary outcome [8]
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Time to first relapse
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Assessment method [8]
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The time to relapse is the time interval from the last point in time when the participant was in the best remission status (either PR or CR) to the first relapse
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Timepoint [8]
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Up until 24 months
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Secondary outcome [9]
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Number of participants who have immunological remission (for anti-PLA2R positive participants)
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Assessment method [9]
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Number of participants who have their anti-PLA2R-Ab level drop below 2 RU/mL who are =14 RU/ml at baseline
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Timepoint [9]
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Up until 24 months
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Secondary outcome [10]
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Number of participants who have a requirement for rescue therapy
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Assessment method [10]
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Number of participants who have a lack of response or relapse at 12 months, and rescue therapies such as obinutuzumab, calcineurin inhibitors, or additional corticosteroid and cyclophosphamide are used.
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Timepoint [10]
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Up until 24 months
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Secondary outcome [11]
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Number of participants who exit the trial
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Assessment method [11]
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Number participant who cease trial follow-up for any reason
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Timepoint [11]
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Up until 24 months
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Secondary outcome [12]
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Quality of life scores (EQ-5D-5L)
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Assessment method [12]
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Quality of life scores using EQ-5D-5L
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Timepoint [12]
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at 3, 6, 9, 12, 15, 18, 24 months
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Secondary outcome [13]
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eGRF slope
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Assessment method [13]
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Change in eGFR slope
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Timepoint [13]
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Up until 24 months
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Secondary outcome [14]
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Number of treatment or PMN associated deaths
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Assessment method [14]
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Number of deaths attributed directly or indirectly to a complication of PMN or the treatment for PMN
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Timepoint [14]
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Up until 24 months
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Secondary outcome [15]
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All cause deaths
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Assessment method [15]
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Number of deaths of any cause
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Timepoint [15]
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Up until 24 months
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Eligibility
Key inclusion criteria
1. Age =18 years.
2. Able to provide informed consent.
3. Primary Membranous Nephropathy (PMN) confirmed by:
1. Kidney biopsy (anti-PLA2R negative patients are eligible for inclusion if PMN is confirmed on biopsy. Kidney biopsy is generally encouraged to confirm diagnosis of PMN) or
2. if the clinician decides against a biopsy, the patient must be anti-PLA2R positive and must not have diabetes.
4. Proteinuria =4 g/24h despite supportive treatment for at least 6 months with maximally tolerated dose of ACE-i or ARB (dose to be stable for at least 4 weeks), confirmed at final screening before randomisation
5. Serum albumin <30 g/L.
6. Estimated glomerular filtration rate (eGFR) =40 ml/min/1.73m2.
7. Treatment with immunosuppression is warranted, as determined by the treating physician.
8. Fully vaccinated against COVID-19 according to local practice/recommendation.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Resistant to rituximab or have had >2 g of rituximab in the past.
2. Resistant to cyclophosphamide or have had a cumulative >20 g of cyclophosphamide in the past.
3. More than 3 years since PMN diagnosis.
4. Proteinuria must not have decreased by >50% over 6 months whilst taking ACE-i/ARB.
5. Patients with human immunodeficiency virus (HIV) infection, active hepatitis B or C infection, or other active infections.
6. Patients with secondary membranous nephropathy
7. Screening for malignancy must be considered especially in cases who are anti-PLA2R negative.
8. Patients whose kidney biopsy shows concomitant features of diabetic nephropathy.
9. Kidney transplant recipients.
10. Pregnancy or breastfeeding.
11. Women of childbearing age not willing to use contraception.
12. Suspected or known hypersensitivity, allergy, and/or immunogenic reaction history to monoclonal antibodies, corticosteroid, cyclophosphamide, any of their ingredients, and any other drugs from these same pharmacotherapeutic groups.
13. Any disorder or condition, in the opinion of the investigator, might pose an unacceptable risk to participant's safety and well-being.
14. Inability to understand or comply with the requirements of the study.
15. Incapable of recognizing the nature, significance, and scope of the clinical trial or giving consent are excluded, even if they have a legal representative.
16. Use of an investigational agent <30 days or within five half-lives of the investigational agents (whichever is longer), whose effect or toxicity may overlap with that of obinutuzumab, prednisolone, cyclophosphamide, or their metabolites.
17. Active Tuberculosis infection. Testing for latent disease may be performed at screening if required by local regulations or in accordance with local clinical practice. Latent disease after completion of appropriate treatment is not exclusionary.
18. Low peripheral B-cell count (as per local reference range) . B-cell count must be checked, particularly in those who have received rituximab, cyclophosphamide or both anytime in the past.
19. Use of SGLT2-i and GLP-1 agonist within 90 days prior to randomisation.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Not yet recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
31/07/2024
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Actual
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/01/2028
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Actual
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Sample size
Target
224
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,TAS,WA
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Recruitment hospital [1]
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Canberra Hospital - Garran
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Recruitment hospital [2]
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Royal Prince Alfred Hospital - Camperdown
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Recruitment hospital [3]
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Sunshine Coast University Hospital - Birtinya
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Recruitment hospital [4]
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Royal Brisbane and Women's Hospital - Brisbane
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Recruitment hospital [5]
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Bundaberg Hospital - Bundaberg
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Recruitment hospital [6]
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Cairns Hospital - Cairns
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Recruitment hospital [7]
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Logan Hospital - Logan
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Recruitment hospital [8]
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Mackay Base Hospital - Mackay
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Recruitment hospital [9]
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Rockhampton Hospital - Rockhampton
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Recruitment hospital [10]
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Mater Hospital - South Brisbane
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Recruitment hospital [11]
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Princess Alexandra Hospital - Woolloongabba
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Recruitment hospital [12]
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Royal Hobart Hospital - Hobart
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Recruitment hospital [13]
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Fiona Stanley Hospital - Murdoch
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Recruitment postcode(s) [1]
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- Garran
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Recruitment postcode(s) [2]
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- Camperdown
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Recruitment postcode(s) [3]
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- Birtinya
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Recruitment postcode(s) [4]
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- Brisbane
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Recruitment postcode(s) [5]
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- Bundaberg
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Recruitment postcode(s) [6]
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- Cairns
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Recruitment postcode(s) [7]
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- Logan
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Recruitment postcode(s) [8]
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- Mackay
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Recruitment postcode(s) [9]
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- Rockhampton
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Recruitment postcode(s) [10]
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- South Brisbane
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Recruitment postcode(s) [11]
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- Woolloongabba
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Recruitment postcode(s) [12]
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- Hobart
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Recruitment postcode(s) [13]
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- Murdoch
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Funding & Sponsors
Primary sponsor type
Other
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Name
The University of Queensland
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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University of Adelaide
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
REMIT is an investigator-initiated, international, multi-centre, prospective, randomised, open-label, parallel-group trial. A total of 224 adult participants with Primary Membranous Nephropathy (PMN) will be recruited from renal units from Australia, New Zealand Canada, Asia, Europe, United Kingdom, and other countries. Participants will be randomised to receive either corticosteroid and cyclophosphamide or obinutuzumab. The primary outcome is a ranked, composite measure based on (a) efficacy, defined as either complete or partial remission of PMN, (b) number of adverse events, and (c) quality of life.
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Trial website
https://clinicaltrials.gov/study/NCT06120673
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Chen Au Peh
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Address
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The University of Adelaide
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Peta-Anne Paul-Brent
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Address
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Country
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Phone
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+61411 397 776
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Data sets will be made available to researchers within the REMIT Study for analysis of sub-studies and country specific outcomes after the primary manuscript has been accepted for publication.
For researchers outside the REMIT study, individual participant data will be made available upon request to a Data Access Committee, a review board set up to assess proposals based on sound science, benefit-risk balancing and research team expertise.
Where data linkage has been used to estimate health care services utilisation, data sharing will be determined by the specific requirements of the data custodians. In some circumstances it may not be possible to share participant level data beyond the country in which it was collected. This will be addressed on a jurisdiction basis.
Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
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When will data be available (start and end dates)?
2 years after publication of pre-specified analyses
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Available to whom?
Data sets will be made available to researchers within the REMIT Study for analysis of sub-studies and country specific outcomes after the primary manuscript has been accepted for publication.
For researchers outside the REMIT study, individual participant data will be made available upon request to a Data Access Committee, a review board set up to assess proposals based on sound science, benefit-risk balancing and research team expertise.
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06120673