Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

December 4, 2023 updated by: West Virginia University
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • WVU Medicine Heart & Vascular Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of Care
Standard of Care treatment
Other: Standard of Care
Standard of Care treatment
Active Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pH
Time Frame: 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.
10 days
Number of Days Alive Free of Stage 2-3 AKI
Time Frame: 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.
28 days post-treatment

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West Virginia University

Investigators

  • Principal Investigator: Ankit Sakhuja, MD, West Virginia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2020

Primary Completion (Actual)

July 15, 2021

Study Completion (Actual)

July 15, 2021

Study Registration Dates

First Submitted

August 20, 2020

First Submitted That Met QC Criteria

August 26, 2020

First Posted (Actual)

August 28, 2020

Study Record Updates

Last Update Posted (Actual)

December 22, 2023

Last Update Submitted That Met QC Criteria

December 4, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005006707

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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