A Uremic Toxin Absorbent (AST-120) to Treat Hospital Acquired Acute Kidney Injury

A Uremic Toxin Absorbent (AST-120) to Treat Hospital Acquired Acute Kidney Injury - A Open Label Randomized Control Trial

Hospital acquired acute kidney injury is an important negative outcome predictor for hospitalized patients. Uremic toxins accumulated after a given renal insult. Some of these uremic toxins are protein bound and may accumulated after renal impairment, owing to both impaired filtration, and inflammation. Recent animal studies have reported that accumulation of uremic toxins, namely indoxyl sulfate and p-cresol, would down regulate endothelial progenitor cells and in turn affect renal recovery. Elimination of these protein bound uremic toxins with an activated charcoal would help restore endothelial function. We will conduct a double blinded randomized placebo controlled trial, which aims to determine that if oral activated charcoal will retard progression of AKI. Also, a panel of markers for endothelial function will also be determined.

Study Overview

• Status: Unknown
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: AST-120and pentoxyphylline (PTX); Drug: pentoxyphylline (PTX)

• Study Type: Interventional
• Enrollment (Anticipated): 206
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tao-Min Huang; Phone Number: 0972655730; Email: taominhuang@gmail.com
• Study Contact Backup: Name: KWAN-DUN WU; Phone Number: 0972651011

Study Locations

• Taiwan
  • Douliou, Taiwan, 640
    • Recruiting
    • National Taiwan University Hospital Yun-Lin Branch
    • Contact: Tao-Min Huang; Phone Number: 0972655730; Email: taominhuang@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

This is a prospective randomized placebo controlled trial. All patients admitted to participating centers with newly diagnosed acute kidney injury (AKI) will be screened for eligibility. The diagnosis of AKI will be determined and staged according to the KIGO-AKI Guideline.11 The inclusion criteria include:

1. Age ≥ 20 years old on the day of admission
2. AKI develops during admission, as defined with KDIGO-AKI Guideline,11 namely, elevation of serum creatinine above 0.3mg/dL within two days, above 1.5times baseline.

Patients with the following conditions will be excluded:

1. Baseline estimated glomerular filtration rates (eGFR) less than 30ml/min/1.73m2 or greater than 90ml/min/1.73m2 according to MDRD equation.
2. Acute kidney injury diagnosed in the indexed admission (according to baseline creatinine)
3. Ileus or under fasting status
4. Previous gastrointestinal operation.
5. Chronic constipation, as defined with bowel movement less than three times a day. If usage of oral laxatives can achieve bowel movement of more than 3 times a day, this patient will not be excluded.
6. Patients had ever undergone any modality of renal replacement therapy (RRT)
7. Patients with major hemorrhage, as defined with requirement of blood transfusion during index admission.
8. Patients with a biopsy proved or clinically diagnosed liver cirrhosis, Child classification B or C.
9. Patients with a congestive heart failure of NYHA Class III or IV, or requirement of inotropic agents.
10. Patients with a chronic lung disease requiring non-invasive or invasive positive pressure ventilation.
11. Solid organ or hematological transplantation donors.
12. Patients who had been diagnosed as AKI in the index hospitalization, as defined with KDIGO 2012 criteria.
13. Patients with oliguric acute kidney injury, as defined with less than 500cc/day.
14. Evidence of obstructive acute kidney injury under kidney echosonography.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AST-120 and PTX; AST-120 2g 4 times a day for 5 days then AST-120 2g 3 times a day for 5 days Pentapentoxifylline 400mg QD for 10 days	Drug: AST-120and pentoxyphylline (PTX); AST-120 2g 4 times a day for 5 days then AST-120 2g 3 times a day for 5 days pentoxyphylline 400mg QD PO x 10 days.
Active Comparator: PTX; Pentapentoxifylline 400mg QD for 10 days	Drug: pentoxyphylline (PTX); pentoxyphylline 400mg QD PO x 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total recovery of kidney function, which is defined as less than 1.5 times pre-morbid creatinine levels on the 10th day of intervention.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total recovery of serum creatinine on Day 5	defined with less than 1.5 times elevation of pre-morbid plasma creatinine level.	5 days
Needing renal replacement therapy on day 10.		10 days
Degree of serum creatinine elevation	as calculated with ratios between highest serum creatinine and pre-morbid creatinine during study period	10 days
The degree of Indoxyl sulfate change on Day 10 (%)		10 days
The degree of Indoxyl sulfate change on Day 5 (%)		5 days
The degree of p-cresol change on Day 10 (%)		10 days
The degree of p-cresol change on Day 5 (%)		5 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: China Medical University Hospital; Chang Gung Memorial Hospital; Taipei Medical University Hospital; National Taiwan University Hospital Hsin-Chu Branch; Taoyuan General Hospital; National Taiwan University Hospital, Yun-Lin Branch
• Investigators: Principal Investigator: YU-SHENG WU, National Taiwan University Hospital; Principal Investigator: Tao-Min Huang, National Taiwan University Hospital, Yun-Lin Branch; Principal Investigator: Wei-Shun Yang, National Taiwan University Hospital Hsin-Chu Branch; Principal Investigator: JUI-HSIANG LIN, Taoyuan General Hospital; Principal Investigator: Ya-Fei Yang, China Medical University Hospital; Principal Investigator: Chan-Yu Lin, Chang Gung Memorial Hospital; Principal Investigator: Heng-Chih Pan, Chang Gung Memorial Hospital; Principal Investigator: Chih-Chin Kao, Taipei Medical University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: January 26, 2016
• First Submitted That Met QC Criteria: February 17, 2016
• First Posted (Estimate): February 22, 2016

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: acute kidney injury; AST-120; indoxylsulfate; p-cresol
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury; 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: 201502003MIPB