Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Acute Kidney Injury Clinical Trial

Official title:

Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04530448
• Other study ID #: 2005006707
• Status: Terminated
• Phase: Phase 4
• Start date: October 5, 2020
• Est. completion date: July 15, 2021

Study information

• Verified date: December 2023
• Source: West Virginia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 15, 2021
• Est. primary completion date: July 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• AKI
• Coronavirus
• Coronavirus Infection
• Coronavirus Infections
• COVID
• Wounds and Injuries

Intervention

Drug:
• 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.

Other:
• Standard of Care
Standard of Care treatment

Locations

Country	Name	City	State
United States	WVU Medicine Heart & Vascular Institute	Morgantown	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
West Virginia University

Country where clinical trial is conducted

United States, 

References & Publications (23)

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Stage 2-3 AKI	proportion of patients developing stage 2-3 AKI (or stage 3 if already at stage 2 at enrollment).	28 days
Secondary	Vent-Free	Ventilator-free days to 28 days	28 days
Secondary	Hospital-Free	Hospital-free days to 60 days	60 days post-index hospitalization

External Links

•   UNITED STATES RENAL DATA SYSTEM