Clinical trial NCT04530448: Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization
Official title: Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: COVID
Coronavirus
Coronavirus Infection
AKI
Acute Kidney Injury
Keywords: Acute Kidney Injury
AKI
COVID-19
Coronavirus
Sodium Bicarbonate
Lead sponsor: West Virginia University
Sponsor class: OTHER
First posted: 2020-08-28
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: pH
timeFrame: 10 days
measure: Number of Days Alive Free of Stage 2-3 AKI
timeFrame: 28 days post-treatment
Secondary outcomes:
measure: Stage 2-3 AKI
timeFrame: 28 days
measure: Vent-Free
timeFrame: 28 days
measure: Hospital-Free
timeFrame: 60 days post-index hospitalization
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: WVU Medicine Heart & Vascular Institute
state: West Virginia
Study officials:
affiliation: West Virginia University
name: Ankit Sakhuja, MD
role: PRINCIPAL_INVESTIGATOR
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