Ignite Creation Date:
2024-05-06 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 12:43 PM
Study NCT ID:
NCT03492255
Status:
TERMINATED
Last Update Posted:
2021-07-21
First Post:
2018-03-16
Brief Title:
CYCLONES - CYClophosphamide LOw Dose and No Extra Steroid
Sponsor:
University of Sao Paulo General Hospital
Organization:
University of Sao Paulo General Hospital
Study Overview
Official Title:
CYCLONES - CYClophosphamide LOw Dose and No Extra Steroid
Status:
TERMINATED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Significative difference between percentage of renal response primary outcome between the two study arms
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CYCLONES
Brief Summary:
Glucocorticoids GC use has increased survival of patients with systemic lupus erythematosus SLE particularly in cases of nephritis and a more significant improvement to 80 with the introduction of therapy combined with immunosuppressants This therapeutic scheme however results in a very high incidence of irreversible damage that is associated in more than 70 of the cases to GC use and in a smaller proportion to the use of high dose cyclophosphamide
CYCLONES is a Controlled Randomized Clinical Trial with the aim of evaluating the efficacy of a regimen for lupus nephritis treatment using only intravenous corticosteroid administration This intravenous corticosteroid regimen has already been tested with Rituximab instead of Cyclophosphamide with high response rates for lupus nephritis and significant reduction of side effects
After selection patients will be randomized in two arms 116 patients will receive Euro-Lupus nephritis regimen and other 116 will undergo treatment with CYCLONES regimen
The primary endpoint is the partial response proteincreatinine ratio 3 with decrease at least of 50 of the initial value and increase of creatinine not higher than 15 of the initial value or complete response proteincreatinine ratio 500 with decrease at least of 50 of the initial value and increase of creatinine not higher than 15 of the initial value in 6 months Secondary outcome measures will be evaluated such as osteoporosis and bone metabolism parameters ophthalmologic evaluation of the collateral effects related to glucocorticoids lipid profile and therapy adherence
CYCLONES is a Controlled Randomized Clinical Trial with the aim of evaluating the efficacy of a regimen for lupus nephritis treatment using only intravenous corticosteroid administration This intravenous corticosteroid regimen has already been tested with Rituximab instead of Cyclophosphamide with high response rates for lupus nephritis and significant reduction of side effects
After selection patients will be randomized in two arms 116 patients will receive Euro-Lupus nephritis regimen and other 116 will undergo treatment with CYCLONES regimen
The primary endpoint is the partial response proteincreatinine ratio 3 with decrease at least of 50 of the initial value and increase of creatinine not higher than 15 of the initial value or complete response proteincreatinine ratio 500 with decrease at least of 50 of the initial value and increase of creatinine not higher than 15 of the initial value in 6 months Secondary outcome measures will be evaluated such as osteoporosis and bone metabolism parameters ophthalmologic evaluation of the collateral effects related to glucocorticoids lipid profile and therapy adherence
Detailed Description:
The use of glucocorticoids GC greatly increased the survival of patients with SLE particularly in cases of nephritis and a more significant improvement to 80 with the introduction of therapy combined with immunosuppressants in the late 1960s This therapeutic regimen however results in a very high incidence of irreversible damage to the patient that is associated in more than 70 of the cases to GC use and in a smaller proportion to the use of a high dose of cyclophosphamide In the last years some less toxic schemes have been proposed The use of low-dose cyclophosphamide has been shown to have equal efficacy as high dose for the induction of remission of lupus nephritis with a fifteen-year follow-up
Regarding GC lower doses of methylprednisolone MP pulse have been shown to have similar efficacy and lower risk of infection In addition retrospective studies have found that high doses of oral GC during the induction period are associated with a higher incidence of side effects without a corresponding increase in efficacy But it was only in 2013 that the first study was published that did not use oral GC in the treatment of lupus nephritis induction with excellent results
In transplantation area there are already several trials minimizing the use of GC proposing in the first days after transplantation the use the methylprednisolone MP IV pulse day 1 500mg day 2 250mg and day 3 125mg followed by oral GC for 4 days 60mg 40mg 30mg and 20mg In this study the same incidence of acute rejection occurred when compared to patients who were treated with oral GC for a prolonged period
Regarding the route of administration of GC it is important to emphasize that MP is three times more active through non-genomic pathway than through genomic pathway which in theory results in a higher efficiency and lower collateral effect when compared to the GC oral route that has similar potency through the two pathways In addition MP has a simpler and dose-proportional pharmacokinetics whereas for oral prednisolone this kinetics is more complex and difficult to predict the dose required to achieve a specific concentration
Therefore the present study intends to evaluate the efficacy and adverse effects of cyclophosphamide EUROLUPUS scheme associated to usual GC dose compared with EUROLUPUS with no extra oral GC regimen
The estimated number of patients was 116 patients for each arm considering an error α 005 and a power 1-β of 80
In moderate flares due to other systemic manifestations the use of a maximum of 20mg day of prednisone for 1 month and a progressive reduction of 5mg every 15 days until withdrawal is allowed Other immunosuppressive biological intravenous immunoglobulin or plasmapheresis will be prohibited
Regarding statistics an Intention-To-Treat ITT analysis will be performed for the randomized patients so that patients presenting side effects or low adherence to treatment will remain in the randomized group and will be evaluated at week 24
The proportion of patients achieving complete and partial remission at week 24 will be compared by the chi-square test or the Fishers exact test as appropriate The same statistical methodology will be applied to compare the number of events listed as secondary endpoints
Regarding GC lower doses of methylprednisolone MP pulse have been shown to have similar efficacy and lower risk of infection In addition retrospective studies have found that high doses of oral GC during the induction period are associated with a higher incidence of side effects without a corresponding increase in efficacy But it was only in 2013 that the first study was published that did not use oral GC in the treatment of lupus nephritis induction with excellent results
In transplantation area there are already several trials minimizing the use of GC proposing in the first days after transplantation the use the methylprednisolone MP IV pulse day 1 500mg day 2 250mg and day 3 125mg followed by oral GC for 4 days 60mg 40mg 30mg and 20mg In this study the same incidence of acute rejection occurred when compared to patients who were treated with oral GC for a prolonged period
Regarding the route of administration of GC it is important to emphasize that MP is three times more active through non-genomic pathway than through genomic pathway which in theory results in a higher efficiency and lower collateral effect when compared to the GC oral route that has similar potency through the two pathways In addition MP has a simpler and dose-proportional pharmacokinetics whereas for oral prednisolone this kinetics is more complex and difficult to predict the dose required to achieve a specific concentration
Therefore the present study intends to evaluate the efficacy and adverse effects of cyclophosphamide EUROLUPUS scheme associated to usual GC dose compared with EUROLUPUS with no extra oral GC regimen
The estimated number of patients was 116 patients for each arm considering an error α 005 and a power 1-β of 80
In moderate flares due to other systemic manifestations the use of a maximum of 20mg day of prednisone for 1 month and a progressive reduction of 5mg every 15 days until withdrawal is allowed Other immunosuppressive biological intravenous immunoglobulin or plasmapheresis will be prohibited
Regarding statistics an Intention-To-Treat ITT analysis will be performed for the randomized patients so that patients presenting side effects or low adherence to treatment will remain in the randomized group and will be evaluated at week 24
The proportion of patients achieving complete and partial remission at week 24 will be compared by the chi-square test or the Fishers exact test as appropriate The same statistical methodology will be applied to compare the number of events listed as secondary endpoints
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