Acute Kidney Injury, AKI, Coronavirus, Coronavirus Infection, COVID
Conditions
Keywords
Acute Kidney Injury, AKI, COVID-19, Coronavirus, Sodium Bicarbonate
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.
Interventions
DRUGSodium 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.
OTHERStandard of Care
Standard of Care treatment
Sponsors
West Virginia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Unable to recruit enough subjects to complete the study. Only 3 subjects enrolled. However, those subjects did not complete the study as the PI terminated the study and data was not collected.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Standard of Care treatment
Standard of Care: Standard of Care treatment | 3 |
| 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.
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. | 0 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 3 | 0 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Sodium Bicarbonate |
|---|---|---|---|
| Age, Continuous | 55 years | 55 years | — |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 0 |
| other Total, other adverse events | 0 / 3 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 0 / 0 |
Outcome results
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.
Time frame: 28 days post-treatment
Population: Unable to recruit enough subjects to complete the study. Only 3 subjects enrolled. However, those subjects did not complete the study as the PI terminated the study and data was not collected.
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.
Time frame: 10 days
Population: Unable to recruit enough subjects to complete the study. Only 3 subjects enrolled. However, those subjects did not complete the study as the PI terminated the study and data was not collected.
Secondary
Hospital-Free
Hospital-free days to 60 days
Time frame: 60 days post-index hospitalization
Population: Unable to recruit enough subjects to complete the study. Only 3 subjects enrolled. However, those subjects did not complete the study as the PI terminated the study and data was not collected.
Secondary
Stage 2-3 AKI
proportion of patients developing stage 2-3 AKI (or stage 3 if already at stage 2 at enrollment).
Time frame: 28 days
Population: Unable to recruit enough subjects to complete the study. Only 3 subjects enrolled. However, those subjects did not complete the study as the PI terminated the study and data was not collected.
Secondary
Vent-Free
Ventilator-free days to 28 days
Time frame: 28 days
Population: Unable to recruit enough subjects to complete the study. Only 3 subjects enrolled. However, those subjects did not complete the study as the PI terminated the study and data was not collected.