Pilot Study to Evaluate Safety, Tolerability, and Performance of the FAST PV Technology™ in Chronic Dialysis Patients

• Sponsor: FAST BioMedical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04733664
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 4.3
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The FAST Plasma Volume (PV) Technology will aid in determining the plasma and interstitial volumes of end stage renal disease patients before and after dialysis therapy, providing a more precise understanding of pre and post dialysis volumes and extent of volume removal during the course of treatment.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease	Device: VFI using the FAST PV Technology	N/A

Detailed Description

This is a pilot, single site, open-label study designed to evaluate the safety, tolerability, and performance of the FAST plasma volume (PV) Technology in dialysis patients.

Administration of VFI will occur within 28 days of screening.

Patients will receive 1 dose of VFI and 1 dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of visible fluorescent injectate (VFI) and iohexol approximately 1 hour after completing dialysis. Patients will be discharged following completion of Day 1 activities. Patients will be seen and evaluated on their next 2 dialysis sessions for any adverse reaction by answering questions about their health, approximately on Day 3 and Day 8. A follow-up phone call will be performed on Day 31 (± 1 day).

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Pilot, Open-Label Study to Evaluate the Safety, Tolerability, and Performance of the FAST PV Technology™ in Chronic Dialysis Patients With Extremely Reduced or No Kidney Function
• Actual Study Start Date: Oct 29, 2020
• Actual Primary Completion Date: Mar 9, 2021
• Actual Study Completion Date: Mar 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis.	Device: VFI using the FAST PV Technology; The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.

Outcome Measures

Primary Outcome Measures

1. Evaluate Plasma Volume (PV) and Interstitial Volume (ISV) Using the FAST PV Technology and Iohexol in Patients on Chronic Dialysis Pre-dialysis [1 day]

   To measure quantitatively the ISV and PV of patients pre dialysis using the FAST PV Technology and iohexol measurement

2. Evaluate Plasma Volume (PV) and Interstitial Volume (ISV) Using the FAST PV Technology and Iohexol in Patients on Chronic Dialysis Post-dialysis [1 day]

   To measure quantitatively the ISV and PV of patients post dialysis using FAST PV Technology and the iohexol measurement

3. Evaluate the Difference in ISV and PV Pre- and Post Dialysis by the FAST PV Technology [1 day]

   Directly compare quantitative difference of ISV and PV measured by the FAST PV Technology to the volume removed during dialysis

4. Evaluate the Difference of ISV and PV Pre- and Post Dialysis by Iohexol [1 day]

   Directly compare quantitative difference of ISV and PV measured by the Iohexol measurement to the volume removed during dialysis

5. The Number of Patients Reporting Any Treatment-emergent Adverse Event. [59 days]

   To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.

6. The Number of Patients Reporting Any Treatment-emergent Serious Adverse Event. [59 days]

   To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.

7. The Number of Patients Reporting Any Drug-related Treatment-emergent Serious Adverse Event. [59 days]

   To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.

8. The Number of Patients Reporting Any Drug Related Treatment-emergent Adverse Event. [59 days]

   To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects/patients must meet all inclusion criteria to be eligible for study participation.

1. Males or females ≥ 18 years of age.

2. Females must be of non-childbearing potential (eg, postmenopausal [defined cessation of regular menstrual periods for at least 1 year confirmed by age => 60 or surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation [documentation required]) or be using a medically acceptable form of birth control (a barrier method, intrauterine device, or hormonal contraception) from screening through 30 days after administration of the last dose of VFI.

3. Males who are sexually active and whose partners are females of childbearing potential must agree to practice abstinence or use condoms from screening through 90 days after administration of the last dose of VFI, and their partners must be willing to use a medically acceptable method of contraception (a barrier method, intrauterine device, or hormonal contraception) from screening through 90 days after administration of the last dose of VFI.

4. Males must agree to not donate sperm from screening through 90 days after administration of the last dose of VFI.

5. Subjects/patients must be able to communicate effectively with the study personnel.

6. Patients must be on chronic hemodialysis for >= 3 months and oliguric defined as <= 2 urinary voids per day.

7. Patients must have an average interdialytic weight gain of at least 2 kg.

8. Patients must have an A-V dialysis shunt.

9. Patients must have a functioning A-V dialysis shunt, either fistula or graft.

Exclusion Criteria Subjects/patients will not be eligible for study participation if they meet any of the exclusion criteria, or will be discontinued at the discretion of the investigator if they develop any of the exclusion criteria during the study.

1. Subject is a pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.

2. History or presence of conditions which, in the judgment of the investigator, are known to interfere with the distribution, metabolism, or excretion of drugs

3. History or presence of conditions that may place the subject/patient at increased risk as determined by the investigator.

4. History of surgery or major trauma within 12 weeks of screening or surgery planned within 4 weeks of the study, including during study participation.

5. Has taken other investigational drugs within 30 days or 5 half-lives of the investigational drug's PK, PD, or biological activity, whichever is longer, prior to first dose of VFI in this study.

6. Prior exposure to VFI or known allergy or hypersensitivity to dextran, 5-aminofluorescein dye, or 2-sulfohexamine rhodamine dye.

7. History of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to iodine, dyes, shellfish, isotopes, or dextran molecules.

8. Significant blood loss (> 450 mL) or has donated 1 or more units of blood or plasma within 4 weeks prior to study participation.

9. Presence of significant hemodynamic instabilities defined as systolic BP <100 on dialysis requiring saline infusion in the past 4 weeks.

10. Presence of ascites and/or 4+ anasarca.

11. Any other condition or prior therapy that, in the investigator's opinion, would make the subject unsuitable for the study, or unable or unwilling to comply with the study procedures.

12. Involved in the planning or conduct of this study.

13. Unwilling or unlikely to comply with the requirements of the study.

14. Clinically significant ongoing bleeding, changing hemoglobin, or experienced significant blood loss within the last 4 weeks.

15. Had a PRBC transfusion in the prior 2 weeks

16. Use of midodrine.

17. Any other condition or prior therapy that, in the investigator's opinion, is likely to deteriorate during study participation

18. Subjects suffering from significant non-cardiac diseases of other organ systems (e. g. Malignancies, significant neurological diseases).

19. Subject has a psychiatric disease or a history of illicit drug use that would prohibit them from complying with study requirements.

20. Use of hemodialysis catheter as primary vascular access for hemodialysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Richard L. Roudebush VA Medical Center	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• FAST BioMedical

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 17, 2020

More Information

Publications

None provided.

• Responsible Party: FAST BioMedical
• ClinicalTrials.gov Identifier: NCT04733664
• Other Study ID Numbers: 2008193898
• First Posted: Feb 2, 2021
• Last Update Posted: Apr 1, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Kidney Failure, Chronic

Study Results

Participant Flow

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 80%
>=65 years	2 20%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	58.5 (5.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 80%
White	2 20%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Evaluate Plasma Volume (PV) and Interstitial Volume (ISV) Using the FAST PV Technology and Iohexol in Patients on Chronic Dialysis Pre-dialysis
Description	To measure quantitatively the ISV and PV of patients pre dialysis using the FAST PV Technology and iohexol measurement
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	10
FAST PV	3869 (805)
FAST ISV	9152 (1701)
Iohexol PV	3895 (801)
Iohexol ISV	19057 (3376)

2. Primary Outcome

Title	Evaluate Plasma Volume (PV) and Interstitial Volume (ISV) Using the FAST PV Technology and Iohexol in Patients on Chronic Dialysis Post-dialysis
Description	To measure quantitatively the ISV and PV of patients post dialysis using FAST PV Technology and the iohexol measurement
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	9
FAST PV	3615 (963)
FAST ISV	7078 (1816)
Iohexol PV	3684 (954)
Iohexol ISV	16770 (4409)

3. Primary Outcome

Title	Evaluate the Difference in ISV and PV Pre- and Post Dialysis by the FAST PV Technology
Description	Directly compare quantitative difference of ISV and PV measured by the FAST PV Technology to the volume removed during dialysis
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	9
FAST PV Difference	343 (376)
FAST ISV Difference	2284 (680)
FAST Total Volume Removed	2628 (904)
Total Volume removed as measured by UF	2451 (604)

4. Primary Outcome

Title	Evaluate the Difference of ISV and PV Pre- and Post Dialysis by Iohexol
Description	Directly compare quantitative difference of ISV and PV measured by the Iohexol measurement to the volume removed during dialysis
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	9
Iohexol PV Difference	340 (380)
Iohexol ISV Difference	2537 (2012)
Iohexol Total Volume Removed	2877 (1940)
Total Volume removed measured by UF	2451 (604)

5. Primary Outcome

Title	The Number of Patients Reporting Any Treatment-emergent Adverse Event.
Description	To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.
Time Frame	59 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	10
Count of Participants [Participants]	8 80%

6. Primary Outcome

Title	The Number of Patients Reporting Any Treatment-emergent Serious Adverse Event.
Description	To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.
Time Frame	59 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	10
Count of Participants [Participants]	3 30%

7. Primary Outcome

Title	The Number of Patients Reporting Any Drug-related Treatment-emergent Serious Adverse Event.
Description	To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.
Time Frame	59 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	10
Count of Participants [Participants]	0 0%

8. Primary Outcome

Title	The Number of Patients Reporting Any Drug Related Treatment-emergent Adverse Event.
Description	To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product.
Time Frame	59 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	10
Count of Participants [Participants]	4 40%

Adverse Events

Time Frame	Enrollment through Discharge, possibly up to 59 days.
Arm/Group Title	Cohort 1
Arm/Group Description	Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. VFI using the FAST PV Technology: The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
All Cause Mortality
	Cohort 1
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Cohort 1
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Gastrointestinal disorders
Gastrointestinal Bleed	1/10 (10%)	1
Vascular disorders
Volume Overload	2/10 (20%)	2
Other (Not Including Serious) Adverse Events
	Cohort 1
	Affected / at Risk (%)	# Events
Total	8/10 (80%)
Gastrointestinal disorders
Nausea	1/10 (10%)	1
General disorders
Dizziness	1/10 (10%)	1
Clotted Fistula	1/10 (10%)	1
Fistula Pseudoaneurysm	1/10 (10%)	1
Infections and infestations
Viral Syndrome	1/10 (10%)	1
Investigations
Elevated CPK	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Leg Pain	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Pruritus	2/10 (20%)	2
Vascular disorders
Hypotension	1/10 (10%)	1
Volume Overload	1/10 (10%)	1

Limitations/Caveats

One patient's PV and ISV were not evaluable post dialysis due to a sampling error.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.