Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03200002 |
| Other study ID # |
LN_CYC_MMF |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
June 20, 2017 |
| Last updated |
June 26, 2017 |
| Start date |
January 1, 2014 |
| Est. completion date |
June 30, 2015 |
Study information
| Verified date |
June 2017 |
| Source |
Chitwan Medical College |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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 (ISN/RPS)
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 0.5 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 < 3.5gms/day if baseline proteinuria >3.5 gms/day or decrease by 50% if baseline
proteinuria <3.5 gms/day) 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.
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
(ISN/RPS) 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 0.5 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 2500/mm3.
Those patients were re-evaluated after one week and intravenous pulse CYC was reinstituted
if the total leucocyte count (TLC) exceeds 2500/mm3. Pulse CYC was administered every month
for a total of six infusions.Patients 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, s/he 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 <1300/mm3 at any study visit; MMF treatment was
discontinued if a patient experienced an absolute neutrophil count <1000/mm3.
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
ACEi/ARBs, other antihypertensives were added as required to achieve target blood pressure
<130/80 mmHg. Oral prednisolone was given at an initial dose of 1 mg/kg with a maximum dose
of 60 mg/day. The starting dose of prednisolone was continued for initial one month. Then,
the dose of oral prednisolone was tapered at the rate of 10 mg/day every 2 weeks and was
maintained at the baseline dose of 5 to 7.5 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.
