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Low Dose Versus High Dose Methylene Blue in Septic Patients

Primary Purpose

Septic Shock

Status
Recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Normal saline
Methylene Blue low dose
Methylene Blue high dose
Sponsored by
National Cancer Institute, Egypt
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients aged ≥ 18 years and ≤ 65 with septic shock as defined by Sepsis-3 criteria (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure (MAP) ≥ 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation), and requiring mechanical ventilation. Exclusion Criteria: myocardial infarction or cerebrovascular accident within the last 3 months. severe lung , liver or kidney disease (creatinine >3.5 mg/dL). pregnancy. glucose 6-phosphate-dehydrogenase deficiency. known allergy to MB or food dyes and the use of nitrates within the last 3 days. more than 24 hrs since initiation of norepinephrine. other causes of shock than sepsis . recent intake (4-weeks) of selective serotonin re-uptake inhibitors or MAOi. refusal of the patient guardian to participate.

Sites / Locations

  • National Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Normal saline

methylene blue low dose

methylene blue high dose

Arm Description

30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours.

30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.

30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.

Outcomes

Primary Outcome Measures

Discontinuation of vasopressor
Time for noradrenaline discontinuation

Secondary Outcome Measures

Mortality
Number of deaths

Full Information

First Posted
August 15, 2023
Last Updated
August 15, 2023
Sponsor
National Cancer Institute, Egypt
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1. Study Identification

Unique Protocol Identification Number
NCT06005558
Brief Title
Low Dose Versus High Dose Methylene Blue in Septic Patients
Official Title
Comparative Study Between High and Low Dose Methylene Blue Infusion in Septic Cancer Patients. A Randomized Blinded Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
January 30, 2024 (Anticipated)
Study Completion Date
February 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Institute, Egypt

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main aim of this study is to examine the various effects of continuous methylene blue infusion in septic cancer patients and to compare it with the traditional infusion of noradrenaline in such patients .
Detailed Description
Exaggerated host response to infection, may result in sepsis, which is life-threatening organ dysfunction . Though considered the number one cause of in-hospital deaths , it can be treatable with early prompt interventions. The 2021 SSC Guidelines use the Third International Consensus definitions, also known as Sepsis-3. Where sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." Organ dysfunction is evidenced by an increased score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA), and septic shock is considered as "a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone." To diagnose septic shock, an euvolemic patient must require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have a lactate level above 2 mmol/L. The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the mainstay of septic shock management. Aim of management is to maintain patient hemodynamically stable until antibiotics kick in and fight infection. In case of non-responders, low dose corticosteroids are prescribed. Other drugs need to be studied to also help in cases of non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide inhibitor that can counteract the vasodilatation in early septic shock. Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the microcirculation. Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of 5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days following the initial bolus dose

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Normal saline
Arm Type
Active Comparator
Arm Description
30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours.
Arm Title
methylene blue low dose
Arm Type
Active Comparator
Arm Description
30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
Arm Title
methylene blue high dose
Arm Type
Active Comparator
Arm Description
30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
Intervention Type
Drug
Intervention Name(s)
Normal saline
Other Intervention Name(s)
Control
Intervention Description
100 ml 0.9% Nacl over 20 minutes, followed by continuous infusion of normal saline for 72 hours.
Intervention Type
Drug
Intervention Name(s)
Methylene Blue low dose
Other Intervention Name(s)
Low dose
Intervention Description
A bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
Intervention Type
Drug
Intervention Name(s)
Methylene Blue high dose
Other Intervention Name(s)
High dose
Intervention Description
A bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
Primary Outcome Measure Information:
Title
Discontinuation of vasopressor
Description
Time for noradrenaline discontinuation
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Mortality
Description
Number of deaths
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged ≥ 18 years and ≤ 65 with septic shock as defined by Sepsis-3 criteria (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure (MAP) ≥ 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation), and requiring mechanical ventilation. Exclusion Criteria: myocardial infarction or cerebrovascular accident within the last 3 months. severe lung , liver or kidney disease (creatinine >3.5 mg/dL). pregnancy. glucose 6-phosphate-dehydrogenase deficiency. known allergy to MB or food dyes and the use of nitrates within the last 3 days. more than 24 hrs since initiation of norepinephrine. other causes of shock than sepsis . recent intake (4-weeks) of selective serotonin re-uptake inhibitors or MAOi. refusal of the patient guardian to participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ehab H Shaker, MD
Phone
01222438820
Email
ehabhanafy2006@yahoo.com
First Name & Middle Initial & Last Name or Official Title & Degree
Mai Elrawas, MD
Phone
01222177242
Email
mai.elrawas@nci.cu.edu.eg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ehab H Shaker, MD
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Institute
City
Cairo
ZIP/Postal Code
12588
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ehab H Shaker, MD
Phone
01222438820
Email
ehabhanafy2006@yahoo.com

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
After study completion and study publication we can share IPD upon request.
Citations:
PubMed Identifier
36505110
Citation
Chalise SN, Sahib TA, Boyer GA, Pathak V. Methylene Blue in Refractory Shock. Cureus. 2022 Nov 6;14(11):e31158. doi: 10.7759/cureus.31158. eCollection 2022 Nov.
Results Reference
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Low Dose Versus High Dose Methylene Blue in Septic Patients

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