Pirfenidone Effect on the Recovery of Renal Function in Septic Acute Kidney Injury

Study Overview
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Brief Summary
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Patients with Septic AKI will be randomized in three arms, group PFD 1,200 will receive PDF 600mg every 12 hrs per mouth, group PDF 600 will receive PFD 600mg in the morning and placebo equivalent at night and Group Placebo will receive placebo every 12 hrs, all for 7 days, all receive conventional treatment KDIGO guides. We analyze the recovery of renal function as a primary objective.

Detailed Description
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Septic acute kidney injury (AKI) is the most common cause of AKI in the world, there is no specific treatment for this pathology; the pathophysiology is related to inflammatory pathway and strategies that modulate this are potentially useful. The Pirfenidone (PDF) is an anti-fibrotic and anti-inflammatory treatment, in animal models has shown a beneficial effect on the recovery of renal function immediately after administrated. The investigators propose a triple blind clinical trial,in which septic AKI patients will be randomized in three arms, all receive conventional treatment KDIGO guides, groupPDF 1,200 will receive PDF 600mg every 12 hrs per mouth, group PDF 600 will receive 600mg in the morning and placebo equivalent at night and Group Placebo will receive placebo every 12 hrs, all for 7 days. The Investigators analyze the recovery of renal function as a primary objective, as a secondary objectives clinical variables associated with renal recovery, biochemical variables, inflammatory, molecular variables and measurement of PDF in blood will be analyzed. Patients will be follow-up for 7 days and 28 days after randomization.

Official Title
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Pirfenidone Effect on the Recovery of Renal Function in Patients With Septic Acute Kidney Injury

Conditions
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Acute Kidney Injury, Sepsis

Intervention / Treatment
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* Drug: Pirfenidone extended release
* Drug: Placebo equivalent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: . sepsis AKI by serum creatinine, according to the KDIGO guide 2012 Acute Kidney Injury • acute on Chronic kidney disease (baseline creatinine <2 mg / dL) Exclusion Criteria: Chronic kidney disease stage 3b, 4 or 5 (basal serum creatinine > 2mg/dl) known and / or sharpened. chronic dialysis (peritoneal dialysis or hemodialysis) History of AKI and / or RRT in the last three months Pregnancy AKI by other causes other than sepsis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Pirfenidone extended release 600mg per mouth every 12 hours for 7 days. | Drug: Pirfenidone extended release<br>* Pirfenidone extended release 600mg per mouth<br>|
| Active Comparator: Group 2<br>Pirfenidone extended release 600mg per mouth in the morning and placebo by night (each treatment every 12 hrs) for 7 days. | Drug: Pirfenidone extended release<br>* Pirfenidone extended release 600mg per mouth<br>Drug: Placebo equivalent<br>* Placebo equivalent per mouth<br>* Other names: Placebo;|
| Placebo Comparator: Group 3<br>Placebo equivalent per mouth every 12 hrs for 7 days. | Drug: Placebo equivalent<br>* Placebo equivalent per mouth<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal function recovery | serum creatinine in serum <2mg/dl and urinary output >1,200 ml/day | within the first 7 days | 
| renal function recovery | serum creatinine in serum <2mg/dl and urinary output >1,200ml/day | within the first 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Volume | Urinary Volume in milliliters in 24 hours | within the first 7 days | 
| need of renal replacement therapy (RRT) | the patient still need renal replacement (RRT) by the judgment of the nephrologist. | within the first 7 days | 
| mortality | the patient dead | within the first 7 days | 
| serum creatinine levels | serum creatinine levels in mg/dL | within the first 7 days | 
| serum urea levels | serum urea levels in mg/dL | within the first 7 days | 
| pirfenidone levels in serum ug/mL | pirfenidone levels in serum ug/mL | on day 1 and day 7 | 
| IL-1 | Interleucin 1 in serum pg/mL | on day 1 and day 7 | 
| IL-6 | Interleucin 6 in serum pg/mL | on day 1 and day 7 | 
| TNF-α | tumor necrosis factor in serum pg/dL | on day 1 and day 7 | 
| Toll-like receptor 4 | Toll-like receptor 4 in serum pg/dL | on day 1 and day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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septic acute kidney injury, pirfenidone