Renoprotection by Pentoxifylline and Angiotensin Receptor Blocker in Chronic Kidney Disease (CKD)

• Status: Unknown status
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, randomized, double-blind, placebo-controlled clinical trial to investigate the renoprotective efficacy of combined pentoxifylline (PTX) and angiotensin receptor blockers (valsartan), compared with placebo and valsartan in 700 patients with Chronic Kidney Disease (CKD) stages 3 and 4. The effect on cardiovascular comorbidity will also be observed. The observation period will be 3 years. The primary endpoints consists of doubling of serum creatinine, end stage renal disease (ESRD), and death from any cause. The secondary endpoints include changes of microalbuminuria or proteinuria, serum and urinary levels of TNF-a(tumor necrosis factor-alpha ), MCP-1(monocyte chemotactic protein), TGF-beta1(transforming growth factor ), collagens III (amino terminal peptide of procollagen III) and IV, and fibronectin, urinary N-acetyl-beta-glucosaminidase, as well as serum fibrinogen and high-sensitive CRP(C reactive protein), and development of heart failure, nonfatal myocardial infarction, and stroke or transient ischemic attack.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Collaborators: Cathay General Hospital; Far Eastern Memorial Hospital; Mackay Memorial Hospital; Shin Kong Wu Ho-Su Memorial Hospital; Taipei Medical University Hospital
• Treatments: Angiotensin Receptor Antagonists; Pentoxifylline

Criteria

Inclusion Criteria:

• Diabetic and non-diabetic men and women between 20 and 80 years of age who have been diagnosed as CKD stage 3 to 4. The diabetic patients must be type II diabetes mellitus (DM) having overt proteinuria or microalbuminuria twice within the preceding 6 months with a clinical exclusion of non-diabetic kidney diseases. Non-diabetic patients may or may not have overt proteinuria; for proteinuric non-diabetic patients, the proteinuria must be present on two occasions within the preceding 6 months.

• Renal replacement therapy is not expected within the forthcoming 12 months.

• Currently under angiotensin receptor blockers(ARB) therapy for at least 8 weeks, with systolic blood pressure<150 mmHg, diastolic blood pressure <90 mmHg

• Renal function has been stable for at least 8 weeks (fluctuation<25% of baseline) at the time of screening

Exclusion Criteria:

• Type I DM patients

• Patients with history of allergy to pentoxifylline or methylxanthine derivatives (such as caffeine, theophylline)or those who have been taking pentoxifylline or dipyridamole as a treatment for chronic disease in the preceding 3 months at screening.

• Patients have been taking ACE inhibitors, renin inhibitors (eg. Rasilez); and direct vasodilators (e.g., hydralazine and minoxidil) at the time of screening

• Females in nursing or pregnancy, or preparing for pregnancy within the next three years.

• Obstructive uropathy.

• Active gastrointestinal bleeding Active peptic ulcer, patients with active bleeding or bleeding tendency and patients under antiplatelet or anticoagulant therapy,except for aspirin 100 mg, clopidogrel 75 mg.

• Unable to stop chronic immunosuppressive therapy or NSAID; or current use of phosphodiesterase inhibitors other than pentoxifylline (eg., dipyridamole)

• Congestive heart failure of functional class III or IV.

• Unstable angina, myocardial infarction, coronary artery bypass graft surgery, or percutaneous coronary intervention, within the past 3 months prior to signing for informed consent.

• Cerebral vascular diseases within the past 3 months prior to signing for informed consent.

• Retinal hemorrhage within the past 3 months prior to signing for informed consent.

• Known or suspected secondary hypertension (e.g., primary aldosteronism, renovascular hypertension, and pheochromocytoma).

• Poor glycemic control (HbA1c>8.5%)

• Liver cirrhosis or hepatic dysfunction as defined by abnormal liver function test

• Biliary obstructive disorders (e.g., cholestasis).

• Active malignancy or infectious diseases.