Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Sponsor

West Virginia University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04530448

Collaborator

(none)

Enrollment

Location

Arms

16.8

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
COVID Coronavirus Coronavirus Infection AKI Acute Kidney Injury	Drug: Sodium bicarbonate Other: Standard of Care	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

Actual Study Start Date :

Oct 5, 2020

Actual Primary Completion Date :

Jul 15, 2021

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	WVU Medicine Heart & Vascular Institute	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

West Virginia University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

UNITED STATES RENAL DATA SYSTEM

Publications

Responsible Party:

Ankit Sakhuja, Assistant Professor of Medicine, Division of Cardiovascular Critical Care, Department of Cardiovascular and Thoracic Surgery, West Virginia University

ClinicalTrials.gov Identifier:

NCT04530448

Other Study ID Numbers:

WVU Protocol #2005006707

First Posted:

Aug 28, 2020

Last Update Posted:

Aug 5, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Ankit Sakhuja, Assistant Professor of Medicine, Division of Cardiovascular Critical Care, Department of Cardiovascular and Thoracic Surgery, West Virginia University

Additional relevant MeSH terms:

Coronavirus Infections

Acute Kidney Injury

Wounds and Injuries

Study Results

No Results Posted as of Aug 5, 2021