Early Metabolic Resuscitation for Septic Shock

Early Metabolic Resuscitation: A Potential Solution to Multi-Organ Dysfunction Syndrome in Septic Shock

This phase II trial studies how well early metabolic resuscitation therapy works in reducing multi-organ dysfunction in patients with septic shock. Early metabolic resuscitation is made of large doses of glucose, protein, and essential metabolic molecules that may help lower the effects of septic shock on the body. Giving patients early metabolic resuscitation in combination with standard of care may work better in reducing multi-organ dysfunction syndrome in patients with septic shock compared to standard of care alone.

Study Overview

• Status: Terminated
• Conditions: Septic Shock; Severe Sepsis; Multiple Organ Failure
• Intervention / Treatment: Other: Best Practice; Dietary supplement: early metabolic resuscitation

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the efficacy of administering early metabolic resuscitation with standard of care (SC + EMR) in patients diagnosed with septic shock for reducing 28-day mortality versus using the standard of care alone (SC).

SECONDARY OBJECTIVES:

I. To assess whether early metabolic resuscitation with standard of care (SC + EMR) is an effective strategy to reduce intensive care unit (ICU) mortality, hospital mortality, and 90-day mortality of septic shock patients relative to SC.

II. To compare the time to death from any cause between patients administered SC + EMR versus SC after being diagnosed with septic shock.

III. To assess whether SC + EMR is an effective strategy to reduce complications of septic shock such as: i) acute kidney injury, ii) dialysis requirements, iii) need for cardiovascular support or days on vasopressors, iv) need for invasive ventilation, days on ventilator support, v) duration of ICU stay, and vi) duration of hospital stay versus SC.

IV. To describe the presence of any adverse effects between the two study groups (SC + EMR group versus [vs] SC group); thus, characterizing their safety.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive standard of care for septic shock.

GROUP II: Patients receive standard of care treatment for septic shock and early metabolic resuscitation (IV) over continuous infusion for up to 7 days.

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

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to the adult medical intensive care unit (MICU).
• Diagnosis of septic shock within 12 hours of ICU admission defined as meeting criteria for sepsis in addition to the following: A) Vasopressor therapy needed to elevate mean arterial pressure (MAP) >= 65 mmg Hg. B) Lactate > 2 mmol/L (18 mg/dL) after adequate fluid resuscitation.
• Sequential Organ Failure Assessment (SOFA) score meeting the following requirements A) Cardiovascular SOFA >= 2 B) Total SOFA score =< 12.
• Patients meeting the above and not able to tolerate enteral nutrition above 70% of their estimated daily caloric need.

Exclusion Criteria:

• Do not resuscitate (DNR).
• Comfort care and end-of-life patients.
• Patients with SOFA scores greater than 12.
• Pregnant women.
• Jehovah Witnesses that do not accept albumin.
• Active bleeding (e.g., gastrointestinal bleeding).
• Acute neurological syndromes (e.g., stroke, hemorrhage, etc.).
• End-stage renal disease (ESRD).

• Chronic liver disease

  • Child-Pugh class C
  • Diagnosis of cirrhosis
• Heart rate less than 50 beats per minute (bpm).
• Respiratory rate less than 8 respirations per minute (rpm).
• Temperature less than 95 degrees Fahrenheit (F) or 35 degrees Celsius (C).
• Tumor lysis syndrome.
• Sulfite allergy: amino acids administration are contraindicated. It is more common in steroid dependent asthmatics. (Please note that this is NOT sulfa allergy and is NOT contraindicated patients with sulfa allergy). Sulfites are present in dried fruits, beer, wines, sausages, jams, maple syrup, and many other food products.
• Serum sodium concentration < 130 mEq/L or > 150 mEq/L (Note: Once serum sodium levels are >= 130 or =< 150 mEq/L within 12 hours after meeting inclusion criteria, the patient can then be considered for the study. This is only a temporary restriction.
• Serum creatinine level: Serum creatinine (SCr) > 2.5 mg/dL (Note: Once serum creatinine levels are =< 2.5 mg/dL within 12 hours after meeting inclusion criteria, the patient can then be considered for the study. This is only a temporary restriction).
• Urine output < 400 cc/24 hours (hrs) plus creatinine > 2.5 mq/dl (Note: Once urine output levels are >= 400 cc within 12 hours after meeting inclusion criteria, the patient can then be considered for the study. This is only a temporary restriction).
• Hyperkalemia K > 5.5 mEq/L (Note: Once potassium levels are =< 5.5 mEq/L within 12 hours after meeting inclusion criteria, the patient can then be considered for the study. This is only a temporary restriction).
• Hyperglycemia: Glucose > 250 mg/dL (Note: Once glucose is below 250 mg/dL within 12 hours after meeting inclusion criteria, the patient can then be considered for the study. This is only a temporary restriction.)
• Hyperphosphatemia: Serum phosphorous > 5.5 mg/dL.
• Patient with a history of metabolic abnormality in any one of the following amino acids: alanine, arginine, cysteine hydrochloride, glycine, histidine, isoleucine, leucine, lysine acetate, methionine, phenylalanine, phosphoric acid, proline, serine, threonine, tryptophan, and valine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group I (standard of care); Patients receive standard of care for septic shock.	Other: Best Practice; Receive standard of care; Other Names: standard of care; standard therapy
Experimental: Group II (early metabolic resuscitation); Patients receive standard of care treatment for septic shock and early metabolic resuscitation (IV) over continuous infusion for up to 7 days.	Other: Best Practice; Receive standard of care; Other Names: standard of care; standard therapy; Dietary supplement: early metabolic resuscitation; Given Intravenous; Other Names: EMR; glucose; hyperalimentation; protein; essential metabolic molecules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 28-day Mortality	To assess the efficacy of administering Early Metabolic Resuscitation with Standard of Care (SC + EMR) in patients diagnosed with septic shock for reducing 28-day mortality versus using the Standard of Care alone (SC). Twenty-eight day mortality is defined during the time from the day SC+EMR or SC was first administered until a patient dies or is followed through 28 days (whichever comes first).	up to 28 days or until death, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 90-Day Mortality	To assess whether Early Metabolic Resuscitation with standard of care (SC + EMR) is an effective strategy to reduce ICU mortality, hospital mortality, and 90-day mortality of septic shock patients relative to SC. ICU mortality is defined as mortality at ICU discharge relative to SC.	up to 90 days or until death, whichever comes first
Number of Participants With Hospital Mortality	To assess whether Early Metabolic Resuscitation with standard of care (SC + EMR) is an effective strategy to reduce hospital mortality of septic shock patients relative to SC.	up to 90 days or until death, whichever comes first
Number of Participants With ICU Mortality	To assess whether Early Metabolic Resuscitation with standard of care (SC + EMR) is an effective strategy to reduce ICU mortality of septic shock patients relative to SC. ICU mortality is defined as mortality at ICU discharge relative to SC.	up to 90-days or until death, whichever comes first

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joseph L. Nates, MBA,MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2019
• Primary Completion (Actual): May 4, 2020
• Study Completion (Actual): May 4, 2020

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Multiple Organ Failure
• Other Study ID Numbers: 2018-0986 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2019-01392 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No