Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05011656
Other study ID # PURIFY Multi-center RCT
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date April 19, 2024
Est. completion date December 30, 2024

Study information

Verified date April 2024
Source ExThera Medical Corporation
Contact Sanja Ilic, M.D.
Phone (925) 839-2060
Email sanja@extheramedical.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is a multi-center, randomized controlled feasibility trial to evaluate the initial safety and efficacy of a novel extracorporeal blood purification (EBP) therapy in critically ill patients with pathogen associated shock across 15 U.S. sites. Adults (18 years old and older) admitted to the ICU with all of the following: • Pathogen associated shock defined as: - The need for vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg despite adequate fluid resuscitation - Presence of a pathogen detected in the bloodstream within 72 hours of screening using commercially available in-vitro diagnostic testing


Description:

Patients meeting the eligibility criteria will be randomized to receive either treatment with the investigational device (Seraph 100) + 'State of the Art' care versus 'State of the Art' care alone. This study is a multi-center, un-blinded, randomized controlled feasibility trial to evaluate the initial safety and efficacy of Seraph 100 in critically ill patients with pathogen associated shock across 15 US sites. This study will not be done in a blinded fashion from either the patient or caregiver perspective given: 1) the need for invasive, central line placement, and 2) to ensure that limited hospital resources (e.g., hemodialysis machines) are available for patients that require therapy. While the study trial will not be conducted in a blinded fashion, the members of the study team that do the data analysis will be blinded. The target population is adults (18 years old and older) admitted to the ICU with all of the following: - Pathogen associated shock AND - The need for vasopressors at any dose to maintain mean arterial pressure (MAP) ≥ 65 mm Hg despite adequate fluid resuscitation. Study Arms: Patients will be randomized to receive either Arm 1: Seraph 100 treatment plus 'State of the Art' or Arm 2: 'State of the Art' care alone. "State of the Art care" will be defined as the treatment algorithms outlined in the Surviving Sepsis Campaign for the treatment of septic shock, available at https://www.sccm.org/SurvivingSepsisCampaign/Home. Study Randomization and stratification: Patients who qualify will be immediately randomized. The study will randomize patients 2:1 to investigational product plus 'State of the Art' care and 'State of the Art' alone, respectively. Upon randomization, patients will be stratified by age (≥65 and <65). While ideally, the research team would stratify by other variables (to include demographics, causative pathogen, GCS, SOFA, associated organ failure, and pre-existing conditions), given the small number of patients in this trial (particularly in the control group) this is not possible. The Seraph 100 Microbind® Affinity Blood Filter (Seraph 100) manufactured by ExThera Medical Corporation in Martinez, CA. Investigational Treatment Duration for Seraph 100: A sufficient blood flow rate and exposure of the patient's blood to the Seraph 100 adsorption media will optimize the treatment success with a target total filtered blood volume of 100L per day. Based on the target total filtered blood volume of 100L, the average treatment duration and blood flow rates are captured below: Average Blood Flow Rate Treatment Duration 350 ml/min 5 hours 300 ml/min 6 hours 250 ml/min 7 hours 200 ml/min 8 hours - At an average blood flow of 350mL/min, this would translate to almost 5 hours of treatment time; an average of 200mL/min would mean a treatment time of 8 hours. - Treatments will occur daily for up to 4 consecutive days or until all of the following criteria are met: - Vasopressor-free for >24h - MAP≥65 - Treatments will be held if subjects are unable to tolerate extra-corporeal therapy (defined as MAP<65 despite fluids and vasopressors) Patients will be assessed daily while hospitalized as part of routine, standard of care in the ICU. All patients enrolled in this study will undergo clinical efficacy, safety, and laboratory assessments. Blood, urine, and respiratory samples will be obtained at baseline, Day 1 (pre/post treatment) through Day 4, Day 7, and Day 28. Demographic and baseline clinical parameters will be recorded at the time of randomization. Pertinent clinical parameters will be recorded hourly for the first 96 hours, once on day 7, and once on day 28. SOFA scores will be recorded daily for the first 7 days. Outcomes data will be recorded on day 28 and at the time of hospital discharge or death. Patient status will be assessed at 30, 60, and 90 days to include vital signs, physical examination, adverse event evaluation, and a targeted medication review. Survival status will be assessed 90 days after enrollment (if the patient is no longer hospitalized). The first 10 patients randomized to interventional therapy, as well as the first 5 patients randomized to the control group, will undergo additional pharmacokinetic (PK) evaluation of antimicrobial removal by the filter treatment. These first 15 total patients enrolled must also meet all requirements for the main portion of the study. As part of the initial PK study, the Data Safety Monitoring Board (DSMB) will also review safety data after the first 5 device patients consented and treated. Safety and PK data will also be reviewed after the first 10 device patients are consented and treated. If there are significant safety concerns after DSMB review, the sponsor will immediately pause the trial and communicate the information with the FDA. The PK results of the first 10 treatment patients will be reported to FDA for review to confirm the proposed dosing prior to commencing enrollment of the remaining subjects for a total of 60 patients.


Recruitment information / eligibility

Status Recruiting
Enrollment 15
Est. completion date December 30, 2024
Est. primary completion date December 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Admitted to an ICU with pathogen associated shock defined as: - The need for vasopressors to maintain mean arterial pressure (MAP) = 65 mmHg despite adequate fluid resuscitation, AND - Presence of a pathogen detected in the bloodstream within 72 hours of screening using commercially available in-vitro diagnostic testing 2. Male or non-pregnant female adult 3. At least 18 years of age at time of enrollment Exclusion Criteria: 1. Pregnant or breast feeding 2. Anticipated transfer to another hospital (that is not a study site) within 72 hours for any reason 3. Not anticipated to survive more than 24 hours 4. Known allergy to heparin sodium 5. Patients who cannot tolerate placement of double-lumen catheter 6. High risk of bleeding (platelet count <50mm3 or International Normalized Ratio (INR) >2) unless adequate line for treatment already placed (e.g. ECMO or RRT/CRRT) 7. Inability to tolerate extracorporeal therapy (defined as MAP<65 despite fluids and vasopressors) 8. Advanced cancer (defined as stage IV) with life expectancy of less than 30 days 9. Unable to obtain informed consent from either patient or legally authorized representative (LAR) 10. Hypotension and volume depletion due to etiologies other than sepsis. 11. Neutropenia with an absolute neutrophil count <500mm3 12. Patients must be treated with one of the antimicrobial agents listed in the Antimicrobial Management Guideline (Table 19). Patients who require treatment with an antimicrobial outside of this list while still receiving treatment with the investigational device must be excluded from the study. 13. If a patient enters the study and later requires a change in the antimicrobial agent used to one which is not listed in the Antimicrobial Management Guideline while still receiving treatment with the investigational device, that patient must be removed from this trial. Clinical data for any patient removed from the trial for this reason will continue to be collected for safety evaluation". 14. Patient is a prisoner or member of a different vulnerable population that should not be included in the study per the investigator or IRB/ethics committee. 15. Advanced directive for "Do Not Resuscitate".

Study Design


Related Conditions & MeSH terms


Intervention

Device:
Seraph-100 + State of the Art Care
Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) manufactured by ExThera Medical Corporation in Martinez, CA. The Seraph 100 filter has been designed and manufactured to reduce residual risks as much as possible to ensure safe usage. Literature search results concluded that heparin-coated medical devices are safe and decrease platelet adhesion without affecting the adsorption of major adhesive proteins. The efficacy, safety, and risk-benefit data of the studies suggest that Seraph 100 is also safe and potentially beneficial by reducing the rate of thrombosis, without its use entailing a risk for patients. The achieved results from the above-mentioned testing and studies support the performance and safety of Seraph 100 consistent with the intended use. ExThera Medical concludes that the known and potential benefits of Seraph 100, when used to treat patients with pathogen associated shock, outweigh the known and potential risks when used according to the intended use.
State of the Art Care
"State of the Art care"is defined as the treatment algorithms outlined in the Surviving Sepsis Campaign for the treatment of septic shock, available at https://www.sccm.org/SurvivingSepsisCampaign/Home

Locations

Country Name City State
United States University of Michigan Ann Arbor Michigan
United States Southeast Georgia Health System, Inc. Brunswick Georgia
United States Good Samaritan Hospital Corvallis Oregon
United States University of Texas Southwestern Medical Center Dallas Texas
United States Trinity Health Mid Atlantic-SMMC Langhorne Pennsylvania
United States Mayo Clinic Rochester Minnesota
United States Methodist Hospital San Antonio Texas
United States University of Texas Health Science Center at San Antonio (UT Health San Antonio) San Antonio Texas
United States George Washington University Washington District of Columbia

Sponsors (2)

Lead Sponsor Collaborator
ExThera Medical Corporation Uniformed Services University of the Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Efficacy - ICU-free days in the first 28 days Alive and not in the ICU (for at least a fulle 24 hours) in the first 28 days from the time of randomization First 28 days
Primary Safety - Adverse Events SAEs and >/= grade 3 AEs per CTCAE v5 evaluated from enrollment until the end of hospitalization Discharge from hospital
Secondary Mortality Evaluate in-hospital mortality and mortality at 28 days 28 days
Secondary Ventilator-free days in the first 28 days Alive and free of mechanical ventilation (for at least a full 24 hours) in the first 28 days from the time of randomization First 28 days
Secondary Vasopressor-free days in the first 28 days Alive and vasopressor-free for at least a 24-hour period in the first 28 days from the time of randomization First 28 days
Secondary Kidney replacement therapy-free days in the first 28 days Alive and not on kidney replacement therapy for at least 72 hours. First 28 days
Secondary Hospital Stay number of days that the subject is hospitalized through study completion, an average of 90 days
Secondary Survival Alive or dead 90 days after enrollment (if discharged from the hospital prior to 90 days after enrollment) through study completion, an average of 90 days
See also
  Status Clinical Trial Phase
Recruiting NCT03649633 - Vitamin C, Steroids, and Thiamine, and Cerebral Autoregulation and Functional Outcome in Septic Shock Phase 1/Phase 2
Terminated NCT04117568 - The Role of Emergency Neutrophils and Glycans in Postoperative and Septic Patients
Completed NCT04227652 - Control of Fever in Septic Patients N/A
Completed NCT05629780 - Temporal Changes of Lactate in CLASSIC Patients N/A
Recruiting NCT04796636 - High-dose Intravenous Vitamin C in Patients With Septic Shock Phase 1
Terminated NCT03335124 - The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock Phase 4
Recruiting NCT04005001 - Machine Learning Sepsis Alert Notification Using Clinical Data Phase 2
Recruiting NCT05217836 - Iron Metabolism Disorders in Patients With Sepsis or Septic Shock.
Recruiting NCT05066256 - LV Diastolic Function vs IVC Diameter Variation as Predictor of Fluid Responsiveness in Shock N/A
Not yet recruiting NCT05443854 - Impact of Aminoglycosides-based Antibiotics Combination and Protective Isolation on Outcomes in Critically-ill Neutropenic Patients With Sepsis: (Combination-Lock01) Phase 3
Not yet recruiting NCT04516395 - Optimizing Antibiotic Dosing Regimens for the Treatment of Infection Caused by Carbapenem Resistant Enterobacteriaceae N/A
Recruiting NCT02899143 - Short-course Antimicrobial Therapy in Sepsis Phase 2
Recruiting NCT02580240 - Administration of Hydrocortisone for the Treatment of Septic Shock N/A
Recruiting NCT02565251 - Volemic Resuscitation in Sepsis and Septic Shock N/A
Recruiting NCT02676427 - Fluid Responsiveness in Septic Shock Evaluated by Caval Ultrasound Doppler Examination
Not yet recruiting NCT02547467 - TOADS Study: TO Assess Death From Septic Shock. N/A
Terminated NCT02335723 - ASSET - a Double-Blind, Randomized Placebo-Controlled Clinical Investigation With Alteco® LPS Adsorber N/A
Completed NCT02638545 - Hemodynamic Effects of Dexmedetomidine in Septic Shock Phase 3
Completed NCT02204852 - Co-administration of Iloprost and Eptifibatide in Septic Shock Patients Phase 2
Completed NCT02079402 - Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care Phase 4