Early Metabolic Resuscitation for Septic Shock

Phase 2

Terminated

• Conditions: Severe Sepsis; Septic Shock; Multiple Organ Failure
• Interventions: Other: Best Practice; Dietary Supplement: early metabolic resuscitation

• Registration Number: NCT03895853
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-03-28
• Study First Submitted QC: 2019-03-28
• Study First Posted: 2019-03-29
• Study Start: 2019-10-04
• Primary Completion: 2020-05-04
• Study Completion: 2020-05-04
• Results First Submitted: 2021-02-02
• Status Verified: 2021-03
• Results First Submitted QC: 2021-03-11
• Results First Posted: 2021-04-08
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (standard of care)	Best Practice	Patients receive standard of care for septic shock.
Group II (early metabolic resuscitation)	Best Practice	Patients receive standard of care treatment for septic shock and early metabolic resuscitation (IV) over continuous infusion for up to 7 days.
Group II (early metabolic resuscitation)	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With 28-day Mortality	up to 28 days or until death, whichever comes first	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With 90-Day Mortality	up to 90 days or until death, whichever comes first	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.
Number of Participants With Hospital Mortality	up to 90 days or until death, whichever comes first	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.
Number of Participants With ICU Mortality	up to 90-days or until death, whichever comes first	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.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States