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

National Taiwan University

Status and phase: Unknown; Phase 3

Conditions: Acute Kidney Injury

Treatments: Drug: AST-120and pentoxyphylline (PTX); Drug: pentoxyphylline (PTX)

Study type: Interventional

Funder types: Other

Identifiers

NCT02687841

201502003MIPB

Details and patient eligibility

About

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.

Enrollment: 206 estimated patients

Sex: All

Ages: 20 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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206 participants in 2 patient groups

AST-120 and PTX

Experimental group

Description:

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

Treatment:

Drug: AST-120and pentoxyphylline (PTX)

PTX

Active Comparator group

Description:

Pentapentoxifylline 400mg QD for 10 days

Treatment:

Drug: pentoxyphylline (PTX)