Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Study Overview
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Brief Summary
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Our overarching goal is to improve the outcomes of critically ill COVID-19 patients with or at risk for development of acute kidney injury (AKI). The objective of this study is to determine the role of a protocol to manage urine alkalization using a simple medication that has been used for a very long time, is safe, and without significant side-effects. We aim to determine the feasibility and safety of a urine alkalinization protocol for the prevention of AKI in patients testing positive for COVID-19.

Detailed Description
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Emerging evidence suggests that acute kidney injury (AKI) secondary to COVID-19 (COV-AKI) might result from direct infection of renal tubule epithelial cells (RTEC). A variety of epithelial cells express the ACE2 receptor which contains the receptor-binding domain (RBD) used by SARS-CoV-1 and SARS-CoV-2 to enter the cells. While direct infection of RTEC has not yet been proven data from multiple laboratories show virus in the kidney. It is this direct viral involvement of the RTEC that this proposal seeks to address. One relatively simple approach would be to perturb the ability of the RBD to bind to its cellular (hACE2) receptor. Changes in pH may cause each amino acid residue, in the RBD, to assume a slightly different 'microscopic' conformation-dependent pKa value. Urine pH is normally 5.5- 6.5 (not too dissimilar to alveolar fluid-6.4-6.86) and can be easily and safely manipulated. In fact, urine alkalinization protocols have been used for decades to reduce renal toxicity from various compounds (especially chemotherapy) and are recommended by US and European toxicology societies. Here, the strategy will be deployed not for ion trapping but to inhibit the virus from infecting RTEC. Alkalinizing the urine using IV sodium-bicarbonate solution to pH of 7.5 or more can be easily and safely achieved. While severe AKI does not appear to be a major part of the SARS-CoV-2 syndrome for most patients, when severe AKI does occur, mortality is very high and preventing early AKI may reduce AKI severity as the disease progresses.

Official Title
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Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Conditions
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COVID, Coronavirus, Coronavirus Infection, AKI, Acute Kidney Injury

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed COVID-19 positive Admission to ICU or step-down unit Age ≥ 18 years old Exclusion Criteria: Stage 3 AKI by KDIGO criteria CKD stage 4-5 Contraindications to Na bicarbonate therapy (e.g. met. alkalosis, severe heart failure) Urine pH > 7.0

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Group 1 (control) will receive standard of care treatment for coronavirus according to institutional protocols. Group 2 (treatment) will receive sodium bicarbonate 225 mEq (225 mL of an 8.4% solution) intravenously over 1 hour.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Standard of Care treatment | Other: Standard of Care<br>* Standard of Care treatment<br>|
| Active Comparator: Sodium Bicarbonate<br>Sodium bicarbonate 225 mEq (225 mL of an 8.4% solution) intravenously over 1 hour. Sodium bicarbonate 8.4% solution should not exceed 900 ml (4 boluses) in 24 hours. | Drug: Sodium bicarbonate<br>* Sodium bicarbonate 225 mEq (225 mL of an 8.4% solution) intravenously over 1 hour. Sodium bicarbonate 8.4% solution should not exceed 900 ml (4 boluses) in 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH | Primary feasibility outcome will be the proportion of patients treated who achieve >50% of urine measurements pH ≥= 7.2 over the duration of treatment. | 10 days | 
| Number of Days Alive Free of Stage 2-3 AKI | Primary efficacy outcome will be the number of days alive and free of stage 2-3 AKI (up to 28) in each group. | 28 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 2-3 AKI | proportion of patients developing stage 2-3 AKI (or stage 3 if already at stage 2 at enrollment). | 28 days | 
| Vent-Free | Ventilator-free days to 28 days | 28 days | 
| Hospital-Free | Hospital-free days to 60 days | 60 days post-index hospitalization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Kidney Injury, AKI, COVID-19, Coronavirus, Sodium Bicarbonate