Early Metabolic Resuscitation for Septic Shock

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03895853
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2
• Location: 1
• Arms: 2
• Actual Duration (Months): 7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Organ Failure; Septic Shock; Severe Sepsis	Other: Best Practice; Dietary Supplement: early metabolic resuscitation	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

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

3. 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.

4. 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 Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Early Metabolic Resuscitation: A Potential Solution to Multi-Organ Dysfunction Syndrome in Septic Shock
• Actual Study Start Date: Oct 4, 2019
• Actual Primary Completion Date: May 4, 2020
• Actual Study Completion Date: May 4, 2020

Arms and Interventions

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: hyperalimentation EMR glucose protein essential metabolic molecules

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Joseph L. Nates, MBA,MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 4, 2020

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT03895853
• Other Study ID Numbers: 2018-0986; NCI-2019-01392; 2018-0986; P30CA016672
• First Posted: Mar 29, 2019
• Last Update Posted: Apr 8, 2021
• Last Verified: Mar 1, 2021

• 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
• Additional relevant MeSH terms: Shock, Septic; Sepsis; Shock; Multiple Organ Failure

Study Results

Participant Flow

Recruitment Details	Recruitment Period: November 2019- December 2019

Arm/Group Title	Intervention Group (EMR Solution)	Controlled Group (Standard Care)
Arm/Group Description	Standard of care + Early metabolic resuscitation	Received standard of care alone
Period Title: Overall Study
STARTED	0	2
COMPLETED	0	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intervention Group (EMR Solution)	Controlled Group (Standard Care)	Total
Arm/Group Description	Standard of care + Early metabolic resuscitation	Received standard of care alone	Total of all reporting groups
Overall Participants	0	2	2
Age (Count of Participants)
<=18 years	0 NaN	0 0%
Between 18 and 65 years	1 Infinity	1 50%
>=65 years	1 Infinity	1 50%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	52	52
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 0%
Male	2 Infinity	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 NaN	0 0%
Not Hispanic or Latino	2 Infinity	2 100%
Unknown or Not Reported	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%
Asian	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%
Black or African American	1 Infinity	1 50%
White	1 Infinity	1 50%
More than one race	0 NaN	0 0%
Unknown or Not Reported	0 NaN	0 0%
Region of Enrollment (participants) [Number]
United States	2 Infinity	2 100%
Cancer Type (Count of Participants)
Gastrointestinal	0 NaN	0 0%	0 0%
Breast	0 NaN	0 0%	0 0%
Lung	0 NaN	1 50%	1 50%
Cancer stage (Count of Participants)
Metastatic Stage	0 NaN	0 0%	0 0%
Localized/Locally advanced	0 NaN	1 50%	1 50%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

No participants participated in the Intervention group.

Arm/Group Title	Intervention Group (EMR Solution)	Controlled Group (Standard Care)
Arm/Group Description	Standard of care + Early metabolic resuscitation	Received standard of care alone
Measure Participants	0	2
Count of Participants [Participants]	0 NaN	0 0%

2. Secondary Outcome

Title	Number of Participants With 90-Day Mortality
Description	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.
Time Frame	up to 90 days or until death, whichever comes first

Outcome Measure Data

Analysis Population Description

No participants participated in the Intervention group.

Arm/Group Title	Intervention Group (EMR Solution)	Controlled Group (Standard Care)
Arm/Group Description	Standard of care + Early metabolic resuscitation	Received standard of care alone
Measure Participants	0	2
Count of Participants [Participants]	0 NaN	0 0%

3. Secondary Outcome

Title	Number of Participants With Hospital Mortality
Description	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.
Time Frame	up to 90 days or until death, whichever comes first

Outcome Measure Data

Analysis Population Description

No participants participated in the Intervention group.

Arm/Group Title	Intervention Group (EMR Solution)	Controlled Group (Standard Care)
Arm/Group Description	Standard of care + Early metabolic resuscitation	Received standard of care alone
Measure Participants	0	2
Count of Participants [Participants]	0 NaN	0 0%

4. Secondary Outcome

Title	Number of Participants With ICU Mortality
Description	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.
Time Frame	up to 90-days or until death, whichever comes first

Outcome Measure Data

Analysis Population Description

No participants participated in the Intervention group.

Arm/Group Title	Intervention Group (EMR Solution)	Controlled Group (Standard Care)
Arm/Group Description	Standard of care + Early metabolic resuscitation	Received standard of care alone
Measure Participants	0	2
Count of Participants [Participants]	0 NaN	0 0%

Adverse Events

Time Frame	baseline, up to 1 year
Adverse Event Reporting Description	No participants were enrolled in the Intervention Group
Arm/Group Title	Intervention Group (EMR Solution)		Controlled Group (Standard Care)
Arm/Group Description	Standard of care + Early metabolic resuscitation		Received standard of care alone
All Cause Mortality
	Intervention Group (EMR Solution)		Controlled Group (Standard Care)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)
Serious Adverse Events
	Intervention Group (EMR Solution)		Controlled Group (Standard Care)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		2/2 (100%)
Metabolism and nutrition disorders
Hypokalemia	/0 (NaN)		2/2 (100%)	7
Other (Not Including Serious) Adverse Events
	Intervention Group (EMR Solution)		Controlled Group (Standard Care)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.