Renal Effect of Pentoxyphylline in High Risk Patients Undergoing Angiography

The investigators will study 2 separate groups:

• Cardiology patients undergoing invasive coronary angiography +/- PCI (Percutaneous coronary intervention).
• Patients undergoing CT examination with contrast medium. All patients will receive intravenous (I.V) hydration for 8-12h before and 36 to 48 h after angiography with 0.45% saline 100ml/h.

All patients will receive oral N-acetyl cysteine 1200 mg twice daily, a day before, on the day of the angiography and for another 48 hours.

In addition, patients will be assigned to receive oral pentoxyphylline (P group) or placebo (C - control group) tablets 3 times a day one day before, on the day of the procedure and for another 48 hours.

Baseline Serum Creatinine (S.Cr) levels in will be taken before angiography and two days after angiography. Radio-contrast nephropathy is defined, in this study, as increase in serum ≥ 25 % of baseline after injection of the radio-contrast agent. Pentoxyfylline is an orally active haemorheological agent for the treatment of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation. Pentoxyfylline acts primarily by increasing red blood cell deformability, by reducing blood viscosity and by decreasing the potential for platelet aggregation and thrombus formation (mechanism unclear). Pentoxyfylline has also proven to have a significant anti inflammatory effect as well as anti oxidant effect, mechanisms considered to be important patho-physiological causes of contrast induced nephropathy.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes Mellitus; Contrast Induced Nephropathy
• Intervention / Treatment: Drug: pentoxyphylline; Drug: placebo; Drug: pentoxiphylline

Detailed Description

Impairment of renal function following exposure to intravenous radio-graphic contrast materials is the third major cause of renal hospital acquired renal dysfunction. Renal dysfunction occurs most often in patients with chronic renal failure and or patients with diabetes mellitus and contributes to the morbidity and mortality. Previous research work proved that the use volume expansion with N-acetyl cysteine (NAC) is superior to volume expiation alone to prevent renal impairment due to radio-contrast5. NAC a potent anti oxidant may prevent CIN by stopping direct oxidative tissue damage and by improving renal hemodynamics.Pentoxyfylline has also proven to have a significant anti inflammatory effect as well as anti oxidant effect.Preangiographic and the highest post-angiographic values of Creatinine and eGFR (estimated glomerular filtration rate) will be recorded. Levels of the biomarker Neutrophil - gelatinase - associated lipocalin (NGAL) will be tested randomly in 49 patients p as a biomarker for contrast induced nephropathy. Blood serology for NGAL will be drown from patients before the procedure and 2 hours after angiography.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Cardiology patients:

1. Hospitalization for ACS (acute coronary syndrome) with NSTEMI or Unstable Angina
2. Diabetic patients (treated with insulin or oral hypoglycemic drugs) or patients with basal serum creatinine greater than 1.3mg/dl in females and 1.5 mg/dl in male patients.
3. Informed consent
4. Age between 18-75

Radiology patients:

1. Radiology patients should be diabetic patients (treated with insulin or oral hypoglycemic drugs) or patients with basal serum creatinine of 1.3mg/dl in females and 1.5 mg/dl in male patients.
2. Informed consent
3. Age between 18-75

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pentoxyphylline cardio; Patients with chronic renal failure (CRF) and/or diabetes mellitus (DM) who are about to go to undergo coronary angiography	Drug: pentoxyphylline; pentoxyphylline tablets, 400 mg per tablet, 3 times a day one day before, on the day of the procedure and for another 48 hours.; Other Names: Oxopurin; Trental; Pentoxifylline-Teva
Placebo Comparator: placebo cardio; Patients with chronic renal failure (CRF) and/or diabetes mellitus (DM) who are about to go to undergo coronary angiography	Drug: placebo; placebo tablets 3 times a day one day before, on the day of the procedure and for another 48 hours.
Experimental: radiology pentoxyphylline; Patients with chronic renal failure (CRF) and/or diabetes mellitus (DM) who are about to go to undergo computed tomography with contrast	Drug: pentoxiphylline; pentoxyphylline tablets, 400 mg per tablet, 3 times a day one day before, on the day of the procedure and for another 48 hours.; Other Names: Pentoxifylline-Teva; terental; oxopurin
Placebo Comparator: radiology placebo; Patients with chronic renal failure (CRF) and/or diabetes mellitus (DM) who are about to go to undergo computed tomography with contrast	Drug: placebo; placebo tablets 3 times a day one day before, on the day of the procedure and for another 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The purpose of the study is to examine the potential renal protective effect of pentoxyphylline in high-risk patients undergoing angiography	The difference between preangiographic and postangiographic values (∆) for S.Cr and eGFR will be calculated and compared between groups. Baseline Serum Creatinine (S.Cr) levels in will be taken before angiography and levels of the biomarker Neutrophil - gelatinase - associated lipocalin (NGAL) will be tested randomly in 49 patients.contrast induced nephropathy. Comparison of the ∆ between the preangiographic and postangiographic values for S.Cr and eGFR will be performed between the groups.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The purpose of the study is to examine the potential renal protective effect of pentoxyphylline in diabetic patients undergoing angiography	Subgroup analysis will be performed for subgroups of patients with diabetes mellitus (DM)	one year
The purpose of the study is to examine the potential renal protective effect of pentoxyphylline in patients with elevated base line creatinin level > 2 undergoing angiography	Subgroup analysis will be performed for subgroups of patients high S.Cr levels before the procedure	one year

Collaborators and Investigators

• Sponsor: Meir Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Anticipated): April 1, 2013
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: June 7, 2010
• First Submitted That Met QC Criteria: June 14, 2010
• First Posted (Estimate): June 15, 2010

Study Record Updates

• Last Update Posted (Estimate): April 8, 2015
• Last Update Submitted That Met QC Criteria: April 7, 2015
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: diabetes mellitus; creatinin level; contrast induced nephropathy; prevention contrast induced nephropathy in high risk patients
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Kidney Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: MMC10059-2010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No