Ignite Creation Date:
2024-05-06 @ 10:15 AM
Last Modification Date:
2024-10-26 @ 12:26 PM
Study NCT ID:
NCT03200002
Status:
COMPLETED
Last Update Posted:
2017-06-28
First Post:
2017-06-20
Brief Title:
Cyclophosphamide Versus Mycophenolate Mofetil in Lupus Nephritis
Sponsor:
Chitwan Medical College
Organization:
Chitwan Medical College
Study Overview
Official Title:
Effect of Cyclophosphamide Versus Mycophenolate Mofetil in Induction Therapy of Lupus Nephritis in Nepalese Population
Status:
COMPLETED
Status Verified Date:
2017-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This was a prospective open label randomized control trial which was conducted for a period of one and half year from January 2014 to June 2015 Out of 52 patients screened 49 patients meeting the international society of nephrology renal pathology society ISNRPS criteria were enrolled in the study comprising of 25 and 24 patients in the cyclophosphamide CYC and mycophenolate mofetil MMF groups respectively Forty two patients 21 in each group could complete the study till the end of 6 months and were included in final analysis Baseline clinical evaluation and investigations were done and recorded CYC was given intravenously as a monthly pulse in the dose of 05 to 1 gram per m2 body surface area MMF was administered in the tablet form with the starting dose of 500 mg twice daily which was increased to 750 mg twice daily after a month Patients were assessed and monitored monthly and the details were recorded Efficacy of treatment was measured as primary end point for those who achieved partial remission reduction of 24 hour urinary protein to 35gmsday if baseline proteinuria 35 gmsday or decrease by 50 if baseline proteinuria 35 gmsday and secondary end point for those who achieved complete remission normalization of serum creatinine and 500 mg of 24 hour urinary protein Adverse events experienced by the patients were also recorded during monthly visit
Detailed Description:
Systemic lupus erythematosus SLE is an autoimmune disease associated with multiple organ involvement among which kidney involvement also known as lupus nephritis LN is quite common in SLE LN is associated with a more than four-fold increase in mortality in patients with SLE The management of SLE and LN comprises timely and coordinated management consisting of initial or induction phase of aggressive immunosuppression to bring the active disease under control followed by maintenance phase The initial phase usually lasting for six months consists of treatment with steroid and cyclophosphamide or mycophenolate mofetil So far there is no study published regarding the efficacy and adverse events of such treatments in Nepal So this study aimed to evaluate and compare the effectiveness and safety profile of mycophenolate mofetil and intravenous pulse cyclophosphamide in induction therapy of LN in Nepalese population
A total of 52 patients with international society of Nephrology renal pathology society ISNRPS class III to V lupus nephritis were screened 3 of which did not meet entry criteria and 49 patients were enrolled in the study comprising of 25 and 24 patients in the MMF and CYC group respectively Twenty one patients in each groups could complete the study till the end of 6 months and were included for analysis
Patients in the CYC group received intravenous cyclophosphamide CYC in the dose of 05 to 1 gram per m2 of body surface area The medicine which is available in the strength of 1 gram in powder form was first dissolved in 20 ml of normal saline Only15 ml of this preparation was mixed in 100 ml of normal saline and was infused over a period of one hour CYC was not given to those patients who had total leukocyte counts TLC less than 2500mm3 Those patients were re-evaluated after one week and intravenous pulse CYC was reinstituted if the total leucocyte count TLC exceeds 2500mm3 Pulse CYC was administered every month for a total of six infusionsPatients were monitored monthly and the details were recorded During follow ups any adverse events in between were noted and detailed physical evaluation was done and all baseline investigations except USG abdomen chest X-ray serum anti nuclear antibody ANA and anti double strain deoxy-ribonuccleic acid anti dsDNA complement factor 3 C3 and complement facotr 4 C4 level was repeated Fasting lipid profile was repeated at the end of third and sixth month of treatment
During the course of treatment if a patient had interruption of medication for less than a 10 days period due to any reason she was considered as a regularly included subject If the interruption extended beyond 10 days the patient was withdrawn from the study
Patients in the MMF group were administered tablet mycophenolate mofetil at a starting dose of 500 mg twice daily if the weight of the patient was less than 50 kilograms and 750 mg twice daily if the weight was more than 50 kilograms After one month the dose of MMF was increased to 750 mg twice daily The clinical response was monitored in terms of reduction in serum creatinine and proteinuria MMF dose was decreased or interrupted in patients experiencing an absolute neutrophil count 1300mm3 at any study visit MMF treatment was discontinued if a patient experienced an absolute neutrophil count 1000mm3
All patients irrespective of randomized group received concomitant corticosteroid therapy with oral prednisolone and hydroxychloroquine Angiotensin receptor inhibitors ACEi angiotensin receptor blocker ARBs were given to all patients if the blood pressure remained above or equal to 120 mmHg of systolic blood pressure and 80 mmHg of diastolic blood pressure If the blood pressure remained persistently high despite the use of ACEiARBs other antihypertensives were added as required to achieve target blood pressure 13080 mmHg Oral prednisolone was given at an initial dose of 1 mgkg with a maximum dose of 60 mgday The starting dose of prednisolone was continued for initial one month Then the dose of oral prednisolone was tapered at the rate of 10 mgday every 2 weeks and was maintained at the baseline dose of 5 to 75 mg per day then after Additional intravenous methylprednisolone was given at the beginning of treatment for patients who presented as rapidly progressive glomerulonephritis RPGN and who had activity index of more than 8 out of 24 on kidney biopsy irrespective of the randomized group MMF or CYC of the patient The dose of methylprednisolone was 1 gram which was given after mixing with 100 ml of normal saline and was infused intravenously over 1 hour for 3 days
A total of 52 patients with international society of Nephrology renal pathology society ISNRPS class III to V lupus nephritis were screened 3 of which did not meet entry criteria and 49 patients were enrolled in the study comprising of 25 and 24 patients in the MMF and CYC group respectively Twenty one patients in each groups could complete the study till the end of 6 months and were included for analysis
Patients in the CYC group received intravenous cyclophosphamide CYC in the dose of 05 to 1 gram per m2 of body surface area The medicine which is available in the strength of 1 gram in powder form was first dissolved in 20 ml of normal saline Only15 ml of this preparation was mixed in 100 ml of normal saline and was infused over a period of one hour CYC was not given to those patients who had total leukocyte counts TLC less than 2500mm3 Those patients were re-evaluated after one week and intravenous pulse CYC was reinstituted if the total leucocyte count TLC exceeds 2500mm3 Pulse CYC was administered every month for a total of six infusionsPatients were monitored monthly and the details were recorded During follow ups any adverse events in between were noted and detailed physical evaluation was done and all baseline investigations except USG abdomen chest X-ray serum anti nuclear antibody ANA and anti double strain deoxy-ribonuccleic acid anti dsDNA complement factor 3 C3 and complement facotr 4 C4 level was repeated Fasting lipid profile was repeated at the end of third and sixth month of treatment
During the course of treatment if a patient had interruption of medication for less than a 10 days period due to any reason she was considered as a regularly included subject If the interruption extended beyond 10 days the patient was withdrawn from the study
Patients in the MMF group were administered tablet mycophenolate mofetil at a starting dose of 500 mg twice daily if the weight of the patient was less than 50 kilograms and 750 mg twice daily if the weight was more than 50 kilograms After one month the dose of MMF was increased to 750 mg twice daily The clinical response was monitored in terms of reduction in serum creatinine and proteinuria MMF dose was decreased or interrupted in patients experiencing an absolute neutrophil count 1300mm3 at any study visit MMF treatment was discontinued if a patient experienced an absolute neutrophil count 1000mm3
All patients irrespective of randomized group received concomitant corticosteroid therapy with oral prednisolone and hydroxychloroquine Angiotensin receptor inhibitors ACEi angiotensin receptor blocker ARBs were given to all patients if the blood pressure remained above or equal to 120 mmHg of systolic blood pressure and 80 mmHg of diastolic blood pressure If the blood pressure remained persistently high despite the use of ACEiARBs other antihypertensives were added as required to achieve target blood pressure 13080 mmHg Oral prednisolone was given at an initial dose of 1 mgkg with a maximum dose of 60 mgday The starting dose of prednisolone was continued for initial one month Then the dose of oral prednisolone was tapered at the rate of 10 mgday every 2 weeks and was maintained at the baseline dose of 5 to 75 mg per day then after Additional intravenous methylprednisolone was given at the beginning of treatment for patients who presented as rapidly progressive glomerulonephritis RPGN and who had activity index of more than 8 out of 24 on kidney biopsy irrespective of the randomized group MMF or CYC of the patient The dose of methylprednisolone was 1 gram which was given after mixing with 100 ml of normal saline and was infused intravenously over 1 hour for 3 days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None