Ignite Creation Date:
2024-05-05 @ 4:57 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00354198
Status:
TERMINATED
Last Update Posted:
2012-11-14
First Post:
2006-07-18
Brief Title:
Efficacy of Pentoxifylline on Rapidly Progressive Glomerulonephritis
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Clinical Efficacy of Combined Pentoxifylline and Conventional Immunosuppressive Regimens on Patients With Rapidly Progressive Glomerulonephritis
Status:
TERMINATED
Status Verified Date:
2012-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
short of participants
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We have recently demonstrated that pentoxifylline PTX has the potential to treat severe glomerular inflammation in a rat model of accelerated anti-glomerular basement membrane GBM glomerulonephritis This study aims to investigate the therapeutic effects of combined PTX and conventional immunosuppressive regimens on patients with rapidly progressive glomerulonephritis
Detailed Description:
Corticosteroids and cytotoxic agents such as cyclophosphamide remain the most commonly used regimens for crescentic glomerulonephritis However their use is often limited by adverse effects most notably life-threatening opportunistic infections due to generalized immunosuppression Over the past decade a number of novel experimental therapeutic agents have been shown to ameliorate the severity of experimental crescentic glomerulonephritis Unfortunately none of these measures is currently available for clinical use Other potential agents such as mycophenolate cyclosporin and tacrolimus while clinically available share similar adverse effects with corticosteroid- and cyclophosphamide-based regimens PTX is a methylxanthine phosphodiesterase inhibitor that has been widely used to treat peripheral vascular diseases and cerebrovascular disorders In addition to its well-known hemorheologic activity accumulating evidence suggests that PTX also possesses potent anti-inflammatory andor immunoregulatory activities For examples PTX has shown its efficacy in different animal models of renal diseases where tumor necrosis factor TNF-alpha monocyte chemoattractant protein MCP-1 or intercellular adhesion molecule-1 is involved Moreover clinical trials in patients with diabetic nephropathy and membranous glomerulonephritis have shown that PTX can lower endogenous TNF-alpha and attenuate proteinuria These data raise the possibility that PTX may have promise as an anti-inflammatory agent via its ability to antagonize inflammatory mediators Consistent with this idea we have demonstrated this potential usefulness of PTX in a rat model of accelerated anti-GBM glomerulonephritis More recently we have reported that PTX is capable of inhibiting proteinuria via renal MCP-1 production in subnephrotic primary glomerular diseases In this study we aim to investigate the potential benefit of combined PTX and conventional immunosuppressive regimens compared to conventional immunosuppressive therapy in patients with rapidly progressive glomerulonephritis
This study is a randomized open-label comparative study Group A is treated by three monthly standard intravenous pulse-dose methylprednisolone 15 mgkgday or a maximum of 1 gday from days 1 to 3 followed by oral prednisolone 05-10 mgkgday from days 4-30 Group B is treated by the same corticosteroid regimen plus intravenous PTX 033-066 mgkgh from days 1 to 7 followed by oral PTX 400-800 mgday from days 8-90 The dose of intravenous PTX will be determined by estimated GFR patients whose GFRs are 30-59 mlmin173 m2 will be given 066 mgkgh and those below 30 mlmin173 m2 will be given 033 mgkgh The oral dose of PTX will also be determined by estimated GFR Patients whose estimated glomerular filtration rates GFRs are between 30-59 mlmin173 m2 will be given 800 mgday and those below 30 mlmin173 m2 will be given 400 mgday If the patients cannot tolerate oral medications either PTX or corticosteroids can be administered intravenously until patients can resume oral intakes Serum and single-voided urine specimens will be collected at the hospital before initiation of therapy day 0 and at days 8 15 30 and 90 after the commencement of therapy Renal function will be calculated by Cockcroft-Gault and simplified Modification of Diet in Renal Disease formula All biochemical and immunological analyses will be performed by the Department of Laboratory Medicine National Taiwan University Hospital Serum and urine samples will be measured for inflammatory mediators using commercial ELISA kits
This study is a randomized open-label comparative study Group A is treated by three monthly standard intravenous pulse-dose methylprednisolone 15 mgkgday or a maximum of 1 gday from days 1 to 3 followed by oral prednisolone 05-10 mgkgday from days 4-30 Group B is treated by the same corticosteroid regimen plus intravenous PTX 033-066 mgkgh from days 1 to 7 followed by oral PTX 400-800 mgday from days 8-90 The dose of intravenous PTX will be determined by estimated GFR patients whose GFRs are 30-59 mlmin173 m2 will be given 066 mgkgh and those below 30 mlmin173 m2 will be given 033 mgkgh The oral dose of PTX will also be determined by estimated GFR Patients whose estimated glomerular filtration rates GFRs are between 30-59 mlmin173 m2 will be given 800 mgday and those below 30 mlmin173 m2 will be given 400 mgday If the patients cannot tolerate oral medications either PTX or corticosteroids can be administered intravenously until patients can resume oral intakes Serum and single-voided urine specimens will be collected at the hospital before initiation of therapy day 0 and at days 8 15 30 and 90 after the commencement of therapy Renal function will be calculated by Cockcroft-Gault and simplified Modification of Diet in Renal Disease formula All biochemical and immunological analyses will be performed by the Department of Laboratory Medicine National Taiwan University Hospital Serum and urine samples will be measured for inflammatory mediators using commercial ELISA kits
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None