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Intravenous DNase I for the Treatment of Sepsis (IDEALSepsisI) (IDEALSepsisI)

Primary Purpose

Sepsis, Critical Illness

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Intravenous DNase I

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age of ≥18 years
Admitted to the ICU in the last 48 hours
Suspected or proven infection as the admitting diagnosis
A sequential (sepsis) organ function assessment (SOFA) score of ≥2 above baseline
Expected to remain in the ICU for ≥ 72 hours

Exclusion Criteria:

No consent/inability to obtain consent from a substitute decision-maker
Have other forms of clinically apparent shock, including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic shock
Have a significant risk of bleeding as evidenced by one of the following:
- Surgery requiring general or spinal anesthesia within 24 hours before enrolment
- The potential need for surgery in the next 24 hours
- Evidence of active bleeding
- A history of severe head trauma requiring hospitalization
- Intracranial surgery, or stroke within three months before the study
- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system
- A history of congenital bleeding diatheses
- Gastrointestinal bleeding within five weeks before the study unless corrective surgery had been performed
- Trauma is considered to increase the risk of bleeding
- Presence of an epidural catheter
- Need for therapeutic anticoagulation
Receiving DNase I by inhalation
Terminal illness with a life expectancy of fewer than three months
Pregnant and/or breastfeeding

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intravenous DNase I

Control

Arm Description

We will enroll up to 36 Participants; each is receiving repeated unit doses of DNase I, BID, delivered by IV infusion over 3 or 7 consecutive days (12 +/- 1 hour apart) according to the following dose-escalation schedule with up to 6 Participants per dose panel. Panel 1: 25 µg/kg, BID for 3 days (cumulative dose: 150 µg/kg) Panel 2: 25 µg/kg, BID for 7 days (cumulative dose: 350 µg/kg) Panel 3: 125 µg/kg, BID for 3 days (cumulative dose: 750 µg/kg) Panel 4: 125 µg/kg, BID for 7 days (cumulative dose: 1750 µg/kg)

We will also enroll 12 septic Participants who do not receive intravenous DNase I (as Comparator Group). These patients will be recruited contemporaneously based on the same inclusion and exclusion criteria.

Outcomes

Primary Outcome Measures

Number of patients recruited per month from the start of the study

Number of patients recruited per month

Number of patients who completed the protocol

The ability to complete study infusion and blood collection as prescribed

Secondary Outcome Measures

Sequential Organ Failure Assessment (SOFA) score

Quantitative variable: Maximal score of SOFA (Sequential Organ Failure Assessment) will be recorded; Value range 0-24 points Delta SOFA score, defined as maximum versus minimum SOFA during ICU stay Change in SOFA score within 48 hours

Organ support free days

Increase of three or more days free from vasopressor therapy, invasive mechanical ventilation or renal replacement therapy.

Duration of ICU admission

Number of days since admission to discharge from the ICU

Time to Hospital discharge

Time elapsed between enrolment into the study (at admission), and discharge

Mortality at Day 90

Number of patients alive at day 90

European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score

Average or median EQ-5D-5L score

Collection of Research Biomarkers related to inflammation and coagulation

Number of patients with all sets of biomarkers

Full Information

NCT ID

NCT05453695

First Posted

June 24, 2022

Last Updated

April 25, 2023

Sponsor

McMaster University

Collaborators

Canadian Institutes of Health Research (CIHR)

1. Study Identification

Unique Protocol Identification Number

NCT05453695

Brief Title

Intravenous DNase I for the Treatment of Sepsis (IDEALSepsisI)

Acronym

IDEALSepsisI

Official Title

Intravenous DNase I for the Treatment of Sepsis: A Phase I Safety and Feasibility Study in ICU Patients

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 2023 (Anticipated)

Primary Completion Date

April 2025 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

McMaster University

Collaborators

Canadian Institutes of Health Research (CIHR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients.

Detailed Description

In sepsis, the release of 'neutrophil extracellular traps' (NETs) by activated neutrophils may contribute to organ damage by acting as scaffolds that trap blood cells and fibrin clots. Excessive NET formation can occlude the vasculature, promoting thrombosis and tissue hypoperfusion. This is a trial on a novel IV therapy for septic patients that shows promise in multiple animal models of sepsis. The therapy, DNase I, is an enzyme that helps to dismantle NETs by digesting cell-free DNA (cfDNA), the major structural component of NETs. The objective of this study is to conduct a Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients. The results of this study may justify a future Phase II trial of the efficacy and safety of DNase I for critically ill patients with sepsis. This trial proposes - To determine the safety, feasibility and maximum tolerated dose (MTD) of using DNase I in septic patients - To evaluate clinical endpoints common in the critically ill such as organ dysfunction severity and trajectory, ICU length of stay, and mortality. - To describe the effects of DNase I on blood coagulation and NETs release - To collect samples for future studies on coagulation and immune function in sepsis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sepsis, Critical Illness

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intravenous DNase I

Arm Type

Experimental

Arm Description

Arm Title

Control

Arm Type

No Intervention

Arm Description

Intervention Type

Drug

Intervention Name(s)

Intravenous DNase I

Intervention Description

Dose-escalating intravenous infusion of DNase I

Primary Outcome Measure Information:

Title

Number of patients recruited per month from the start of the study

Description

Number of patients recruited per month

Time Frame

up to 24 months

Title

Number of patients who completed the protocol

Description

The ability to complete study infusion and blood collection as prescribed

Time Frame

up to 7 days

Secondary Outcome Measure Information:

Title

Sequential Organ Failure Assessment (SOFA) score

Description

Time Frame

Baseline to Day 10

Title

Organ support free days

Description

Increase of three or more days free from vasopressor therapy, invasive mechanical ventilation or renal replacement therapy.

Time Frame

at Day 28

Title

Duration of ICU admission

Description

Number of days since admission to discharge from the ICU

Time Frame

up to 9 months

Title

Time to Hospital discharge

Description

Time elapsed between enrolment into the study (at admission), and discharge

Time Frame

up to 90 days

Title

Mortality at Day 90

Description

Number of patients alive at day 90

Time Frame

up to day 90

Title

European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score

Description

Average or median EQ-5D-5L score

Time Frame

At day 90

Title

Collection of Research Biomarkers related to inflammation and coagulation

Description

Number of patients with all sets of biomarkers

Time Frame

up to day 14

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age of ≥18 years Admitted to the ICU in the last 48 hours Suspected or proven infection as the admitting diagnosis A sequential (sepsis) organ function assessment (SOFA) score of ≥2 above baseline Expected to remain in the ICU for ≥ 72 hours Exclusion Criteria: No consent/inability to obtain consent from a substitute decision-maker Have other forms of clinically apparent shock, including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic shock Have a significant risk of bleeding as evidenced by one of the following: Surgery requiring general or spinal anesthesia within 24 hours before enrolment The potential need for surgery in the next 24 hours Evidence of active bleeding A history of severe head trauma requiring hospitalization Intracranial surgery, or stroke within three months before the study Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system A history of congenital bleeding diatheses Gastrointestinal bleeding within five weeks before the study unless corrective surgery had been performed Trauma is considered to increase the risk of bleeding Presence of an epidural catheter Need for therapeutic anticoagulation Receiving DNase I by inhalation Terminal illness with a life expectancy of fewer than three months Pregnant and/or breastfeeding

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alison Fox-Robichaud, MD

Phone

905 521 2100

Ext

4074

afoxrob@mcmaster.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Patricia Liaw, PhD

Phone

(905) 521-2100

Ext

40788

Patricia.Liaw@taari.ca

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Intravenous DNase I for the Treatment of Sepsis (IDEALSepsisI)

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