VBI-S for the Treatment of Hypotension in Hypovolemic Septic Shock Patients

This study is being conducted to evaluate the safety and effectiveness of VBI-S in elevating the blood pressure of septic shock patients with absolute or relative hypovolemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis; Septic Shock; Hypovolemia
• Intervention / Treatment: Drug: VBI-S

Detailed Description

PURPOSE OF THE STUDY This study is being conducted to evaluate the safety and effectiveness of VBI-S in elevating the blood pressure of septic shock patients with absolute or relative hypovolemia.

STUDY TREATMENT Sepsis is a serious condition resulting from the presence of harmful microorganisms in the blood or other tissues and the body's response to their presence, leading to the malfunctioning of various organs. When hypotension due to sepsis cannot be reversed with the infusion of fluids the patient is in a state of septic shock. Septic shock is therefore an acute medical emergency and delayed therapy can lead to organ injury. VBI-S is intended to raise blood pressure in patients with septic shock.

Randomization and blinding: This is an open label study, randomization and blinding are not applicable to this study. All patients entering this study will be treated with VBI-S.

Data Safety Monitoring Board: A Data Safety Monitoring Board (DSMB) will review the study data.

Analysis Populations: * Safety Analysis Set (SAF): all patients who have received any amount of VBI-S. * Intent to treat (ITT) population: all patients who have received any amount of VBI-S

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cuthbert O Simpkins, MD, FACS; Phone Number: (318) 771-1294; Email: cuthbert@vivacellebio.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Dignity Health
    • Tucson, Arizona, United States, 85719
      • University of Arizona
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • UMD Shock Trauma
    • Silver Spring, Maryland, United States, 20904
      • Adventist Health Care
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • Pennsylvania
    • East Norriton, Pennsylvania, United States, 19403
      • Einstine Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Male or female at least 18 years of age
2. Evidence of bacterial infection demonstrated by positive blood culture and/or a known source of infection or an elevated procalcitonin of ≥ 2 ng/ml.
3. Patient has a mean blood pressure < 65 mmHg that is unresponsive to fluids currently available on the market.
4. Sequential Organ Failure Assessment (SOFA) score >= 5.

5. Sepsis diagnosis: The presence of infection which can be proven or suspected by 2 or more of the following criteria:

   • Lactate > 2 mmol/L
   • Mottled skin
   • Decreased capillary refill of nail beds or skin
   • Fever > 38.3˚C, or 101˚F
   • Hypothermia < 36˚C core temperature (<96.8˚F)
   • Heart rate > 90
   • Tachypnea
   • Change in mental status
   • Significant edema or positive fluid balance (>20 mL/kg over 24 hours)
   • Hyperglycemia (>140 mg/dL) in someone without diabetes
   • White blood cell count >12,000 or less than 4,000, or with >10% "bands" (immature
   • forms)
   • Elevated C-reactive protein in serum (according to your lab's cutoffs)
   • Elevated procalcitonin in serum (≥ 2 ng/ml)
   • Arterial hypoxemia (PaO2/FiO2 < 300)
   • Acute drop in urine output (<0.5 ml/kg/hr for at least 2 hours despite fluid resuscitation, or about 30 ml/hour for a 70 kg person)
   • Creatinine increase > 0.5 mg/dL
   • INR > 1.5 or aPTT > 60 seconds
   • Absent bowel sounds (ileus)
   • High bilirubin (total bilirubin > 4 mg/dL

Exclusion Criteria:

1. Patients with a ventricular assist device
2. Acute coronary syndrome
3. Pregnant
4. Bronchospasm
5. Mesenteric ischemia
6. Emergency surgery
7. Acute liver disease (Hepatitis B and C as examples)
8. Liver failure with a Model for End-Stage Liver Disease (MELD) score ≥ 19
9. Hematologic or coagulation disorders including thrombocytopenia (platelet count <50,000) and associated with hemodynamically significant active bleeding.
10. Absolute neutrophil count of < 1000 mm3
11. Current participation or participation in another experimental or device study within the last 30 days before the start of this study. Patient may be included if on other drugs for COVID-19 and or septic shock
12. Patients with a known allergy to soybeans or eggs
13. Patient is hypervolemic as assessed by CVP, ultrasound, Swan Ganz catheter, Flo-Trac, esophageal doppler, bioimpedance, ECHO, Partial carbon dioxide rebreathing (NICO), lithium dilution (LIDCO) or other method published in a peer reviewed journal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Treatment with VBI-S	Drug: VBI-S; VBI-S is made of small particles of specific lipid called micelles and liposomes for the treatment of hypotension.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint of this study is the proportion of patients in whom mean blood pressure increased by at least 10 mmHg with a mean blood pressure target of 60 - 65 mmHg.	The primary endpoint of this study is the proportion of patients in whom mean blood pressure increased by at least 10 mmHg with a mean blood pressure target of 60 - 65 mmHg.	10 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary endpoint of this study is the proportion of patients in whom the dose of pressor drugs could be decreased after infusion of VBI-S to maintain a mean arterial pressure of 60-65 mmHg	The secondary endpoint of this study is the proportion of patients in whom the dose of pressor drugs could be decreased after infusion of VBI-S to maintain a mean arterial pressure of 60-65 mmHg	10 Months

Collaborators and Investigators

• Sponsor: Vivacelle Bio
• Investigators: Principal Investigator: Cuthbert Simpkins, MD, FACS, Vivacelle Bio

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Hypotension; Hypovolemia
• Other Study ID Numbers: VBI-S-01

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