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Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Primary Purpose

COVID, Coronavirus, Coronavirus Infection

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sodium bicarbonate
Standard of Care
Sponsored by
West Virginia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID focused on measuring Acute Kidney Injury, AKI, COVID-19, Coronavirus, Sodium Bicarbonate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • WVU Medicine Heart & Vascular Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Standard of Care

Sodium Bicarbonate

Arm Description

Standard of Care treatment

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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

Full Information

First Posted
August 20, 2020
Last Updated
August 4, 2021
Sponsor
West Virginia University
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1. Study Identification

Unique Protocol Identification Number
NCT04530448
Brief Title
Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization
Official Title
Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 5, 2020 (Actual)
Primary Completion Date
July 15, 2021 (Actual)
Study Completion Date
March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West Virginia University

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, Coronavirus, Coronavirus Infection, AKI, Acute Kidney Injury
Keywords
Acute Kidney Injury, AKI, COVID-19, Coronavirus, Sodium Bicarbonate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
Standard of Care treatment
Arm Title
Sodium Bicarbonate
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sodium bicarbonate
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Standard of Care treatment
Primary Outcome Measure Information:
Title
pH
Description
Primary feasibility outcome will be the proportion of patients treated who achieve >50% of urine measurements pH ≥= 7.2 over the duration of treatment.
Time Frame
10 days
Title
Number of Days Alive Free of Stage 2-3 AKI
Description
Primary efficacy outcome will be the number of days alive and free of stage 2-3 AKI (up to 28) in each group.
Time Frame
28 days post-treatment
Secondary Outcome Measure Information:
Title
Stage 2-3 AKI
Description
proportion of patients developing stage 2-3 AKI (or stage 3 if already at stage 2 at enrollment).
Time Frame
28 days
Title
Vent-Free
Description
Ventilator-free days to 28 days
Time Frame
28 days
Title
Hospital-Free
Description
Hospital-free days to 60 days
Time Frame
60 days post-index hospitalization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
WVU Medicine Heart & Vascular Institute
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Links:
URL
https://www.usrds.org/
Description
UNITED STATES RENAL DATA SYSTEM

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Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

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