Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Phase 4

Terminated

Conditions: COVID
Coronavirus
AKI
Coronavirus Infection
Acute Kidney Injury

Interventions: Other: Standard of Care
Drug: Sodium bicarbonate

Registration Number: NCT04530448

Lead Sponsor: West Virginia University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Standard of Care treatment
Sodium Bicarbonate	Sodium bicarbonate	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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