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Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04530448
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Ankit Sakhuja, West Virginia University

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization
Actual Study Start Date : October 5, 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : March 2021


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.




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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).

  2. Vent-Free [ Time Frame: 28 days ]
    Ventilator-free days to 28 days

  3. Hospital-Free [ Time Frame: 60 days post-index hospitalization ]
    Hospital-free days to 60 days



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530448


Contacts
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Contact: Ankit Sakhuja, MD 304.598.6092 ankit.sakhuja@hsc.wvu.edu
Contact: Lisa Fornaresio, PhD lisa.fornaresio@wvumedicine.org

Locations
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United States, West Virginia
WVU Medicine Heart & Vascular Institute Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Ankit Sakhuja, MD       ankit.sakhuja@hsc.wvu.edu   
Contact: Lisa Fornaresio, PhD       lisa.fornaresio@wvumedicine.org   
Principal Investigator: Ankit Sakhuja, MD         
Sub-Investigator: Paul McCarthy, MD         
Sponsors and Collaborators
West Virginia University
Additional Information:
Publications:

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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: August 28, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Ankit Sakhuja, West Virginia University:
Acute Kidney Injury
AKI
COVID-19
Coronavirus
Sodium Bicarbonate
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Acute Kidney Injury
Wounds and Injuries
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases