Comparison of efficacy and safety of intravenous cyclophosphamide and steroids with oral cyclophosphamide and steroids in the treatment of idiopathic membranous nephropathy
Aim of the study is to assess the efficacy of intravenous cyclophosphamide as compared to oral cyclophosphamide in the treatment of primary membranous nephropathy.
Secondary objective is to document side effects of both regimens
Design
Two arm parallel unblinded, Randomized control trial. Sample size is 58. 29 patient in each group.
Randomization will be done by lottery method. It will be a singe center study.
Settings and conduct
Indoor and out patient department of Nephrology department of Jinnah hospital. It will be non blinded study.
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
1. Serum Anti-Phospho Lipase A2 Receptor positive or IgG4 positivity on Immunofluorescence.
2. Biopsy–proven Idiopathic Membranous Nephropathy high risk group (Spot Urine protein/ spot urine creatinine Ratio more than 8g/g).
3. Biopsy –proven Idiopathic Membranous Nephropathy, moderate risk group that has failed to respond to conservative therapy for 6 months.
Exclusion Criteria:
1. Patients with clinical, histologic, or serologic evidence of secondary Membranous Nephropathy.
2. Active or ongoing infection/ Recent infection.
3. Allergy or contraindication to cyclophosphamide.
Intervention groups
Patients will be assigned into two groups randomly. Non probability / consecutive sampling
technique will be used. One group will be given intravenous cyclophosphamide, 500mg/m2 on 2, 4 and 6
months and steroid on 1, 3 and 5 month as per modified ponticelli regimen. Control group will
be given oral cyclophosphamide 2 mg/kg/day on 2, 4 and 6 months and steroids on 1,3 and 5
months as per modified ponticelli regimen.
Main outcome variables
Spot urinary protein: creatinine ratio.
Serum creatinine.
Side effects like anemia, thrombocytopenia, leucopenia, any infection or hospitalization and malignancy.
General information
Reason for update
Acronym
CIMNT (Cyclophosphamide in membranous nephropathy trial)
IRCT registration information
IRCT registration number:IRCT20230517058211N1
Registration date:2023-07-18, 1402/04/27
Registration timing:registered_while_recruiting
Last update:2023-07-18, 1402/04/27
Update count:0
Registration date
2023-07-18, 1402/04/27
Registrant information
Name
Fazle Mateen
Name of organization / entity
Allama Iqbal medical college/ Jinnah hospital Lahore
Country
Pakistan
Phone
+92 321 4027280
Email address
fazal.mateen@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-06-01, 1402/03/11
Expected recruitment end date
2024-05-30, 1403/03/10
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of efficacy and safety of intravenous cyclophosphamide and steroids with oral cyclophosphamide and steroids in the treatment of idiopathic membranous nephropathy
Public title
Intravenous and oral cyclophosphamide in membranous nephropathy
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Serum Anti-Phospho Lipase A2 Receptor positive or IgG4 positivity on Immunofluorescence.
Biopsy –proven Idiopathic Membranous Nephropathy, moderate risk group (Spot Urine protein/ spot urine creatinine Ratio between 4 to 8 g/g) that has failed to respond to conservative therapy for 6 months.
Biopsy–proven Idiopathic Membtanous Nephropathy high risk group (Spot Urine protein/ spot urine creatinine Ratio more than 8g/g).
Exclusion criteria:
Patients with clinical, histologic, or serologic evidence of secondary Membranous Nephropathy.
Evidence of Hepatitis B/C and Human Immunodeficiency Virus
Evidence of malignancy (Prostate Specific Antigen, Mammogram, Chest x-ray.)
Active or ongoing infection/ Recent infection.
Allergy to cyclophosphamide.
Contraindication to steroid/ cyclophosphamide
Age
From 18 years old to 80 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
58
Randomization (investigator's opinion)
Randomized
Randomization description
Patients will be assigned into two groups randomly by lottery method. Lottery method will be. Non probability / consecutive sampling technique will be used. The researcher randomly picks envelops for each with numbers, with each number corresponding to a subject in order to create the sample. To create a sample this way, the researcher must ensure that the numbers are well mixed before selecting the sample population.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethical review board, Allama Iqbal Medical College/ Jinnah hospital, Lahore
Street address
Allama Shabir Ahmad usmai Road, Lahore .
City
Lahore
Postal code
544550
Approval date
2023-03-31, 1402/01/11
Ethics committee reference number
ERB141/8/31-03-2023/S1ERB
Health conditions studied
1
Description of health condition studied
Primary Membranous Nephropathy
ICD-10 code
N04.2
ICD-10 code description
Nephrotic syndrome with diffuse membranous glomerulonephritis
Primary outcomes
1
Description
Reduction in proteinuria calculated by spot urine protein: creatinine ratio less than 0.2
Timepoint
Monthly for 6 months after starting treatment, then monthly follow up after 6 months of completion of treatment. Total 12 months
Method of measurement
Spot urine sample will be send to lab
Secondary outcomes
1
Description
Hemoglobin
Timepoint
Monthly for 6 months after starting treatment (duration of treatment 6 months), then monthly follow up after 6 months of completion of treatment. Total 12 months
Method of measurement
Blood sample
2
Description
White cell count
Timepoint
Monthly for 6 months after starting treatment (duration of treatment 6 months), then monthly follow up after 6 months of completion of treatment. Total 12 months
Method of measurement
Blood sample
3
Description
Reduction in Serum Creatinine
Timepoint
Monthly for 6 months after starting treatment (duration of treatment 6 months), then monthly follow up after 6 months of completion of treatment. Total 12 months
Method of measurement
Blood sample
Intervention groups
1
Description
Intervention group: Intravenous cyclophosphamide 500mg/m2 on 2, 4 and 6 months. Injection Cyclophosphamide wil be given as infusion of 100 ml saline over 1 hour. Before infusion patient's cell count and C Reactive protein (CRP) will be checked. In months 1, 3 and 5 Injection Methypredisolone 1gram intravenously once a day for first 3 days, then Tab Prednisolone 0.5 mg/Kg body weight will be given in two divided doses for next 27 days.Total treatment wil be of six months
Category
Treatment - Drugs
2
Description
Control group: Oral cyclophosphamide 2mg/kg in two divided doses on 2,4 and 6 months. Before cyclophosphamide treatment patient's cell count and C Reactive protein (CRP) will be checked. In months 1, 3 and 5 Injection Methypredisolone 1gram intravenously once a day for first 3 days, then Tab Prednisolone 0.5 mg/Kg body weight will be given in two divided doses for next 27 days. Total treatment wil be of six months
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Nephrology department, Jinnah Hospital, Lahore
Full name of responsible person
Dr Muhammad Saleem
Street address
Allama Iqbal Medical College,Allama Shabir Ahmad Usmani Road, Lahore
City
Lahore
Postal code
54550
Phone
+92 332 8376745
Email
saleemdr5@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Jinnah Hospital/ Allama Iqbal Medical College
Full name of responsible person
Dr Muhammad Saleem
Street address
Jinnah Hospital , Allama Shabir Ahmad Usmani Road, Faisal Town
City
Lahore
Postal code
54550
Phone
+92 332 8376745
Email
saleemdr5@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Jinnah Hospital/ Allama Iqbal Medical College
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Jinnah Hospital/ Allama Iqbal Medical College
Full name of responsible person
Dr Muhammad Saleem
Position
Consultant Nephrologist
Latest degree
Specialist
Other areas of specialty/work
Nephrology
Street address
Jinnah Hospital , Allama Shabir Ahmad Usmani Road, Faisal Town
City
Lahore
Province
Punjab
Postal code
54550
Phone
+92 332 8376745
Email
saleemdr5@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Jinnah Hospital/ Allama Iqbal Medical College
Full name of responsible person
Dr Muhammad Saleem
Position
Consultant Nephrologist
Latest degree
Specialist
Other areas of specialty/work
Nephrology
Street address
Jinnah Hospital , Allama Shabir Ahmad Usmani Road, Faisal Town
City
Lahore
Province
Punjab
Postal code
54550
Phone
+92 332 8376745
Email
saleemdr5@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Jinnah Hospital/ Allama Iqbal Medical College
Full name of responsible person
Dr Fazl e Mateen
Position
Assistant Professor
Latest degree
Specialist
Other areas of specialty/work
Nephrology
Street address
Jinnah Hospital , Allama Shabir Ahmad Usmani Road, Faisal Town
City
Lahore
Province
Punjab
Postal code
54550
Phone
+92 332 8376745
Email
saleemdr5@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
No - There is not a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
Intravenous versus oral cyclophosphamide in Primary Membranous Nephropathy.
Data will be availale in Excel sheets of all participants of study including their primary and secondary outcomes
When the data will become available and for how long
Data about the participants of both arms and their outcomes will be available
Data will be available after May 2024 and it will be available 6 months after publication
To whom data/document is available
Only for doctors working in teaching institutes
Under which criteria data/document could be used
Data can only be used by health professionals for research purposes
From where data/document is obtainable
Data will be available through email: saleemdr5@gmail.com
What processes are involved for a request to access data/document
Person who needs data should ask for permission of usage of data through email provided. Email should include name, position held, teaching institute and purpose of using data.
Comments
Our study data will be available for any ongoing study if needed