Multi-Center Trial Utilizing Low Frequency Ultrasound in the Prevention of Post-Contrast Acute Kidney Injury (LOTUS)

Low Frequency Therapeutic Ultrasound System Pivotal Clinical Trial

Multi-center randomized trial to assess the safety and performance of low-frequency therapeutic ultrasound for maintaining renal function after contrast exposure.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Diseases; Contrast-induced Nephropathy
• Intervention / Treatment: Device: Low-frequency therapeutic ultrasound (LOTUS); Device: LOTUS System with Ultrasound Disabled

Detailed Description

This is a multi-center, randomized, controlled clinical trial designed to assess the safety and performance of the Sonogenix RENOBOOST as an adjunctive therapy for maintaining renal function after contrast exposure. The trial will enroll up to 234 subjects not taking oral nitrates and at high-risk of developing PC-AKI undergoing coronary arteriography for a planned percutaneous coronary intervention in up to 10 clinical sites in the US and up to 3 clinical sites outside the US.

All subjects will be pre- treated with 0.9 percent NaCl at 3 ml/kg/h 1 hour before and 1 ml/kg/h during and 6 hours post procedure. Participants will be randomized in a 2:1 fashion to either active adjunctive therapy with the Sonogenix RENOBOOST or sham control.

Subjects will have clinical follow-up examination 30 days post index procedure.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katy Feeny, BME; Phone Number: 419-787-8496; Email: kjclinconsulting@gmail.com
• Study Contact Backup: Name: Tiffini Wittwer, MPH; Phone Number: 707-799-6732; Email: twittwer@mededge.io

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hopsital
    • Petoskey, Michigan, United States, 49770
      • McLaren Northern Michigan
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pennsylvania Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant is greater than or equal to 18 years

• Baseline renal dysfunction defined as one of the following:

  1. eGFR greater than 30
  2. eGFR 30-45, with or without risk factors for AKI defined as diabetes mellitus, congestive heart failure, proteinuria (defined as albuminuria greater than 300mg/day).
  3. eGFR 45-60, with at least one risk factor for AKI defined as diabetes mellitus, congestive heart failure, proteinuria (defined as albuminuria greater than 300mg/day).
• Participant is presenting for a planned percutaneous coronary intervention (PCI)
• Participant scheduled to undergo cardiac catheterization including coronary arteriography that is anticipated to require at least 100 ml of iso-osmolar or low- osmolar contrast, and that is anticipated to include single-vessel stent implantation that does not include chronic total occlusion.
• Participant had not been hospitalized or treated for a change in renal function within 30 days of enrollment.
• Participant has provided written informed consent.
• Participant is willing to comply with study follow-up requirements.

Exclusion Criteria

• Participant is anuric or currently undergoing renal replacement therapy.
• Participant is currently taking oral nitrates.
• Participant is undergoing a procedure requiring selective cannulation and injection of contrast into the renal arteries.
• Participant presented with ST-segment elevation myocardial infarction.
• Participant has a metal implant in the hip or lumbar spine.
• Participant received or is anticipated to receive additional intravenous or intraarterial contrast from 7 days prior to cardiac catheterization to 4 days after cardiac catheterization.
• Addition, discontinuation, or dose change of angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, diuretic, trimethoprim, non-steroidal anti-inflammatory drugs, cimetidine, or metoclopramide with 7 days prior to cardiac catheterization.
• Participant has a known allergy to contrast medium that cannot be adequately pre-medicated.
• Participant has new-onset heart failure with New York Heart Association (NYHA) classification of III or IV within 30 days prior to the index procedure.
• Recent stroke within 90 days prior to the index procedure.
• Participant has known or suspected active infection at the time of the index procedure.
• Participant is pregnant and/or breast-feeding or intends to become pregnant during the time of the study.
• Participant is unwilling or unable to comply with procedures specified in the protocol or has difficulty or inability to return for follow-up visits as specified by the protocol.
• Participant is known to be incarcerated, mentally incompetent, and/or alcohol or drug abuser.
• Participant is participating in another investigational drug or medical device study that has not completed primary endpoint(s) evaluation or clinically interferes with the endpoints from this study or subject is planning to participate in such studies prior to the completion of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Frequency Therapeutic Ultrasound; LOTUS system will be operated per operated per normal instructions	Device: Low-frequency therapeutic ultrasound (LOTUS); Participants will wear low-frequency therapeutic ultrasound system for procedure. Device will be turned on per normal operating instructions.
Sham Comparator: Sham Control; LOTUS system will be set to Control setting	Device: LOTUS System with Ultrasound Disabled; Participants will wear low-frequency therapeutic ultrasound system for procedure. Device will be turned on and set to Control Setting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint	Incidence of acute kidney injury (AKI) defined as a greater than 0.3 mg/dl increase in serum creatinine (SCr)	48 hours
Primary Safety Endpoint	Composite of all Adverse Events (AE) including RENOBOOST (device) related adverse events, and major adverse events (MAE)	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Post Contrast Acute Kidney Injury	defined as greater than or equal to 0.3 mg/dl or greater than or equal to 25 percent rise in SCr	at 72 hours post-contrast exposure or need for renal replacement therapy (RRT)
Incidence of Post Contrast Acute Kidney Injury	defined as greater than or equal to 0.5 mg/dl or greater than or equal to 25 percent rise in SCr	at 72 hours post-contrast exposure or need for renal replacement therapy (RRT)
Incidence of contrast-induced nephropathy	defined as greater than or equal to 0.3 mg/dl or greater than or equal to 25 percent rise in SCr	within 96 hours post-contrast exposure or need for RRT
Occurrence of (stage 1, 2, or 3) acute kidney injury (AKI)	defined as greater than or equal to 2-fold rise in SCr, increase in SCr to greater than or equal to 4.0 mg/dl, or initiation of RRT	within 30 days after index procedure
Incidence of Post Contrast Acute Kidney Injury	defined as greater than or equal to 0.3 mg/dl or greater than or equal to 25 percent rise in SCr	within 96 hours post-contrast exposure or need for RRT
Occurrence of (stage 1, 2, or 3) acute kidney injury (AKI)	defined as Stage 1 - Serum Creatinine 1.5-1.9 times baseline or greater than or equal to 0.3 mg/dL increase, Stage 2 - Serum Creatinine 2-2.9 times baseline, Stage 3 - Serum Creatinine 3 times baseline or Increase in serum creatinine to greater than or equal to 4 mg/dL or Initiation of renal replacement therapy	within 96 hours of index procedure
Maximum percent-change	Maximum percent-change in SCr	within 96 hours after contrast exposure
Absolute and percent-change in estimated glomerular filtration rate (eGFR)	as calculated using the Modification of Diet in Renal Disease Study Group (MDRD)	from baseline within 96 hours after contrast exposure.
Total urine output	defined as the amount of urine collected in cc/hour.	through baseline procedure
Hospitalization	Hospital length of stay	following the baseline procedure through discharge from the hospital up to 30 days
Intensive Care	Intensive care unit length of stay	following the baseline procedure through discharge from the Intensive Care Unit up to 30 days

Collaborators and Investigators

• Sponsor: Sonogenix

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2021
• Primary Completion (Actual): January 23, 2023
• Study Completion (Actual): January 23, 2023

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: nitric oxide; coronary arteriography
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: CP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes