Use of CRRT increased during COVID and remained at these higher utilization levels

Study results demonstrate challenges physicians have with heparin and citrate, the two currently available CRRT anticoagulants 

SAN MATEO, Calif., Dec. 12, 2023 /PRNewswire/ -- AcelRx Pharmaceuticals, Inc. (NASDAQ: ACRX), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings, today announced the publication of a quantitative market research study evaluating current U.S. physician anticoagulation use during continuous renal replacement therapy (CRRT) in patients with acute kidney injury in the intensive care unit.  The only FDA-approved anticoagulant for dialysis circuits is heparin, which has a half-life of 1-3 hours. Heparin is therefore classified as a "systemic" anticoagulant, as it circulates back into the patient from the dialysis circuit, resulting in anticoagulation of the patient, which is often dangerous. The FDA has given an Emergency Use Authorization (EUA) to citrate, which is classified as a "regional" anticoagulant, as its effect is reversed with a calcium infusion that is administered to the patient, therefore limiting its anticoagulant effect to the circuit.

The publication, entitled "Anticoagulation Practices for Continuous Renal Replacement Therapy: A Survey of Physicians from the United States," is lead authored by Dr. David Boldt, and published in the journal Renal Failure.  Dr. Boldt is an Associate Professor at the University of California, Los Angeles School of Medicine, Critical Care Intensivist and Division Chief of Trauma and Adult Multi-Specialty Anesthesiology. In the study, a total of 150 U.S. board-certified physicians consisting of critical care medicine specialists (n=80) and nephrologists (n=70) who specialize in CRRT were surveyed by MedSurvey from November to December 2022 regarding their current CRRT anticoagulation practices.

 This study resulted in a number of key findings:

  • CRRT machine use increased by approximately 30% from pre-pandemic era to late 2022.
  • On average, physicians use heparin in the CRRT circuit for 43% of patients, with citrate being used in 28% of patients and no anticoagulation used in 29% of patients.
  • The top reason for use of heparin is that it is readily available, but concerns with heparin included systemic bleeding and heparin-induced thrombocytopenia, which were ranked 3.5 and 3.4 respectively, on a 1-5 scale of "not challenging" to "very challenging".
  • Hypocalcemia (52% of physicians) and citrate safety (42% of physicians) were ranked as the top two reasons for not using citrate in heparin-intolerant patients. Physicians who do use citrate reported that hypocalcemia occurs in 37% of patients.
  • When no anticoagulation is used in the CRRT circuit, 84% of physicians stated filter clogging was a problem and almost a quarter of the physicians stated an increase in transfusions was required as a result.

Study limitations include that the study was an online survey; however, physicians had to pass eight screening questions to ensure they were board-certified in critical care medicine or nephrology, worked in an ICU, and were familiar with the protocols and logistics of CRRT use in their hospital.

"It is clear from this study that physicians in charge of CRRT at their institutions are not completely satisfied with the currently available anticoagulants, heparin and citrate, for use in the dialysis circuit," stated Dr. Pamela Palmer, AcelRx Chief Medical Officer and co-founder. "Niyad as a potentially new regional anticoagulant for patients who cannot tolerate heparin could provide a meaningful improvement to the current standard of care in this field. Allowing physicians to avoid the complexities associated with citrate and reducing the number of patients who receive no anticoagulation by offering a new alternative can hopefully improve the quality of CRRT for these very fragile patients."

Dr. Boldt states, "We really don't have any great choices as it relates to CRRT anticoagulation, which is why I am excited about the potential approval of Niyad as a new anticoagulant option. Nafamostat's ultra short half-life of 8 minutes and its limited systemic effect could really change how we approach anticoagulation of CRRT circuits. Heparin is fraught with potentially significant, and often life-threatening, complications such as systemic bleeding and heparin-induced thrombocytopenia, as well as heparin resistance, all of which make using heparin challenging in many patients." Dr. Boldt continues, "While citrate avoids the risk of systemic bleeding, its complicated administration protocol, requirement for a calcium infusion, frequent testing of calcium levels, and citrate toxicity risks can lead many clinicians to avoid its use altogether."

AcelRx provided funding to conduct the study. Some of the authors, including Dr. Boldt, are consultants for AcelRx but were not paid for their contributions to this manuscript.

About AcelRx Pharmaceuticals

AcelRx Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings. AcelRx's lead product candidate, Niyad™ is a lyophilized formulation of nafamostat and is currently being studied under an investigational device exemption, or IDE, as an anticoagulant for the extracorporeal circuit, and has received Breakthrough Device Designation status from the FDA. AcelRx is also developing two pre-filled syringes in-licensed from its partner Aguettant: Fedsyra™, a pre-filled ephedrine syringe, and PFS-02, a pre-filled phenylephrine syringe. This release is intended for investors only. For additional information about AcelRx, please visit www.acelrx.com.

About Nafamostat

Nafamostat is a broad spectrum, synthetic serine protease inhibitor with anticoagulant, anti-inflammatory and potential anti-viral activities. Niyad™ is a lyophilized formulation of nafamostat and is currently being studied under an investigational device exemption, or IDE, as an anticoagulant for the extracorporeal circuit, and has received Breakthrough Device Designation Status from the FDA. LTX-608 is a proprietary nafamostat formulation for direct IV infusion that will be investigated and developed as a potential anti-viral for the treatment of COVID, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute pancreatitis.

Forward-looking statements

This press release contains forward-looking statements based upon AcelRx's current expectations. These and any other forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking terminology such as "potential", "believe", "expect", "expects", "expected", "anticipate", "hopefully",  "upcoming", "may", "will", "enable", "should", "seek", "approximately", "intends", "intended", "plans", "planned", "planning", "estimates", "benefits", or the negative of these words or other comparable terminology. The discussion of strategy, plans or intentions may also include forward-looking statements, which are predictions, projections and other statements about future events that are based on current expectations and assumptions. These forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those projected, anticipated or implied by such statements, including: (i) risks relating to AcelRx's product development activities and ongoing commercial business operations; (ii) risks related to the ability of AcelRx and its business partners to implement development plans, launch plans, forecasts and other business expectations; (iii) risks related to unexpected variations in market growth and demand for AcelRx's commercial and developmental products and technologies; (iv) risks related to AcelRx's liquidity and its ability to maintain capital resources sufficient to conduct the required clinical studies; (v) AcelRx's ability to retain its listing on the Nasdaq exchange; and (vi) risks relating to AcelRx's ability to obtain regulatory approvals for its developmental product candidates. Although it is not possible to predict or identify all such risks and uncertainties, they may include, but are not limited to, those described under the caption "Risk Factors" and elsewhere in AcelRx's annual, quarterly and current reports (i.e., Form 10-K, Form 10-Q and Form 8-K) as filed or furnished with the Securities and Exchange Commission (SEC) and any subsequent public filings. You are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date such statements were first made. To the degree financial information is included in this press release, it is in summary form only and must be considered in the context of the full details provided in AcelRx's most recent annual, quarterly or current report as filed or furnished with the SEC. AcelRx's SEC reports are available at www.acelrx.com under the "Investors" tab. Except to the extent required by law, AcelRx undertakes no obligation to publicly release the result of any revisions to these forward-looking statements to reflect new information, events or circumstances after the date hereof, or to reflect the occurrence of unanticipated events.

For additional information about AcelRx, please visit www.acelrx.com.

This release is intended for investors only.

AcelRx logo. (PRNewsFoto/AcelRx Pharmaceuticals, Inc.) (PRNewsfoto/AcelRx Pharmaceuticals, Inc.)

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SOURCE AcelRx Pharmaceuticals, Inc.

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