Trial record 1 of 224 for:    "Glomerulonephritis"
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Efficacy of Pentoxifylline on Rapidly Progressive Glomerulonephritis

This study has been terminated.
(short of participants)
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00354198
First received: July 18, 2006
Last updated: November 12, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Glomerulonephritis
Drug: pentoxifylline
Drug: corticosteroids
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Efficacy of Combined Pentoxifylline and Conventional Immunosuppressive Regimens on Patients With Rapidly Progressive Glomerulonephritis

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • initiation of acute dialysis or doubling of serum creatinine levels [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • end-stage renal disease (ESRD) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: August 2006
Study Completion Date: June 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: corticosteroids
[intravenous pulse methylprednisolone (15 mg/kg/day or a maximum of 1 g/day) x 3 days + oral prednisolone (0.5-1.0 mg/kg/day) for 27 days] x 3 courses
Drug: corticosteroids
intravenous methylprednisolone (15 mg/kg/day or a maximum of 1 g/day) x 3 days + oral prednisolone (0.5-1.0 mg/kg/day) for 27 days] x 3 courses
Other Name: Solu-medrol, Predonin
Experimental: pentoxifylline + corticosteroids
[intravenous pulse methylprednisolone (15 mg/kg/day or a maximum of 1 g/day) x 3 days + oral prednisolone (0.5-1.0 mg/kg/day) for 27 days] x 3 courses + intravenous infusion of pentoxifylline (0.33-0.66 mg/kg/h) x 7 days + oral pentoxifylline (400-800 mg/day) from days 8 to 90
Drug: pentoxifylline
intravenous pentoxifylline (0.33-0.66 mg/kg/h from days 1 to 7) followed by oral pentoxifylline 400-800 mg/day (from days 8-90). The dose of intravenous pentoxifylline will be determined by estimated GFR, patients whose GFRs are 30-59 ml/min/1.73 m2 will be given 0.66 mg/kg/h, and those below 30 ml/min/1.73 m2 will be given 0.33 mg/kg/h. The oral dose of pentoxifylline will also be determined by estimated GFR. Patients whose estimated GFRs are between 30-59 ml/min/1.73 m2 will be given 800 mg/day, and those below 30 ml/min/1.73 m2 will be given 400 mg/day.
Other Name: Trental
Drug: corticosteroids
intravenous methylprednisolone (15 mg/kg/day or a maximum of 1 g/day) x 3 days + oral prednisolone (0.5-1.0 mg/kg/day) for 27 days] x 3 courses
Other Name: Solu-medrol, Predonin

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 and/or 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 mg/kg/day or a maximum of 1 g/day from days 1 to 3) followed by oral prednisolone 0.5-1.0 mg/kg/day (from days 4-30). Group B is treated by the same corticosteroid regimen plus intravenous PTX (0.33-0.66 mg/kg/h from days 1 to 7) followed by oral PTX 400-800 mg/day (from days 8-90). The dose of intravenous PTX will be determined by estimated GFR, patients whose GFRs are 30-59 ml/min/1.73 m2 will be given 0.66 mg/kg/h, and those below 30 ml/min/1.73 m2 will be given 0.33 mg/kg/h. The oral dose of PTX will also be determined by estimated GFR. Patients whose estimated glomerular filtration rates (GFRs) are between 30-59 ml/min/1.73 m2 will be given 800 mg/day, and those below 30 ml/min/1.73 m2 will be given 400 mg/day. 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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • biopsied-proved crescentic glomerulonephritis, with rapidly progressive renal failure

Exclusion Criteria:

  • Anti-GBM disease, Dialysis-dependency or pulmonary hemorrhage, History of allergy to pentoxifylline, Females are nursing or pregnant, Congestive heart failure, Unstable angina, myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, within the past 6 months prior to signing the informed consent form, Cerebral hemorrhage within the past 6 months prior to signing the informed consent form, Retinal hemorrhage within the past 6 months prior to signing the informed consent form, Known or suspected secondary hypertension, Uncontrolled hypertension or diabetes, Liver cirrhosis or hepatic dysfunction as defined by liver enzymes > 2 times the upper limit of the normal range, Biliary obstructive disorders, Active malignancy or infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354198

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Yung-Ming Chen, M.D. NTUH
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00354198     History of Changes
Other Study ID Numbers: 941008
Study First Received: July 18, 2006
Last Updated: November 12, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
rapidly progressive glomerulonephritis
pentoxifylline

Additional relevant MeSH terms:
Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases
Methylprednisolone
Pentoxifylline
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Hematologic Agents
Radiation-Protective Agents
Vasodilator Agents
Cardiovascular Agents
Free Radical Scavengers
Antioxidants

ClinicalTrials.gov processed this record on August 28, 2014