Trial Outcomes & Findings for Immunomodulatory Properties of Ketamine in Sepsis (NCT NCT01089361)

NCT ID: NCT01089361

Last Updated: 2017-08-21

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 19 participants
• Primary outcome timeframe: first 7 days of admission, Baseline and Day 7 reported
• Results posted on: 2017-08-21

Participant Flow

Patients were recruited between 2009 and 2010 from the ICU.

All patients who consented were randomized to treatment or placebo.

Participant milestones

Measure	Normal Saline The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Overall Study STARTED	9	10
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Normal Saline The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Overall Study Death	1	0

Baseline Characteristics

Immunomodulatory Properties of Ketamine in Sepsis

Baseline characteristics by cohort

Measure	Normal Saline n=9 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	63 years STANDARD_DEVIATION 19 • n=5 Participants	60 years STANDARD_DEVIATION 11 • n=7 Participants	61 years STANDARD_DEVIATION 15 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: first 7 days of admission, Baseline and Day 7 reported

Outcome measures

Measure	Normal Saline n=8 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Serum Levels of IL-6, IL-10 and TNFα Baseline IL-10	28 pg/mL Interval 8.1 to 246.9	16 pg/mL Interval 12.2 to 19.6
Serum Levels of IL-6, IL-10 and TNFα Day 7 IL-10	9.3 pg/mL Interval 4.7 to 12.9	6.3 pg/mL Interval 5.0 to 10.5
Serum Levels of IL-6, IL-10 and TNFα Baseline IL-6	3227.7 pg/mL Interval 512.0 to 7205.7	613.8 pg/mL Interval 320.8 to 3190.5
Serum Levels of IL-6, IL-10 and TNFα Day 7 IL-6	322.8 pg/mL Interval 96.8 to 428.0	266.2 pg/mL Interval 56.3 to 285.8
Serum Levels of IL-6, IL-10 and TNFα Baseline TNF-alpha	2.5 pg/mL Interval 1.5 to 6.2	7.1 pg/mL Interval 3.2 to 7.9
Serum Levels of IL-6, IL-10 and TNFα Day 7 TNF-alpha	2 pg/mL Interval 1.2 to 3.1	6.3 pg/mL Interval 2.4 to 15.4

SECONDARY outcome

Timeframe: 7 days

Outcome measures

Measure	Normal Saline n=9 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Adverse Effects Attributable to Ketamine	0 adverse events	2 adverse events

SECONDARY outcome

Timeframe: 7 days

Incidence of new organ failure as detected by Sequential Organ Failure Assessment [SOFA] score. Definitions are as follows. Central nervous system: delirium, coma, uncontrollable seizures, ICP>20cm H2O Cardiac: MAP <60mmHg, blood pressure supported with pressors, 50 > HR > 120 Respiratory: vented, RR>30, PaO2<60, PaCO2 > 55, Sat<92% Kidney: RIFLE criteria Anemia: Hct<27, transfusion of PRBC Thrombocytopenia: platelet < 50k, platelet transfusion Liver: biopsy, ALT>200, AST>200, t.bil>2.0, ALP>300 Coagulation failure: INR>2 if no anticoagulation therapy

Outcome measures

Measure	Normal Saline n=9 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Organ Failures	3 participants with increase in SOFA score	2 participants with increase in SOFA score

SECONDARY outcome

Timeframe: First 24 hours after ICU admission

Difference in average APACHE-II score between the intervention and placebo groups. APACHE II (Acute Physiology and Chronic Health Evaluation II) is a severity of disease classification system for patients admitted to the Intensive Care Unit. It uses an integer score from 0 to 71 that is computed based on age, 12 routine physiological measurements (i.e. heart rate, temperature, laboratory values), and previous health status obtained during the first 24 hours after ICU admission. Higher scores correspond to more severe disease and a higher risk of death.

Outcome measures

Measure	Normal Saline n=9 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Acute Physiology and Chronic Health Evaluation (APACHE) Scores	25 APACHE score Standard Deviation 8	23 APACHE score Standard Deviation 10

SECONDARY outcome

Timeframe: 28 days

Outcome measures

Measure	Normal Saline n=8 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Length of Intensive Care Unit (ICU) Stay	19 days Standard Deviation 9	20 days Standard Deviation 9

SECONDARY outcome

Timeframe: 28 days

Outcome measures

Measure	Normal Saline n=9 Participants The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 Participants The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
28 Day Mortality	4 deaths	2 deaths

OTHER_PRE_SPECIFIED outcome

Timeframe: Daily up to 7 days

Population: Not done

PCR analysis on serum samples for presence of bacterial and mitochondrial DNA; This substudy was not done.

Outcome measures

Measure	Normal Saline The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
PCR Substudy	0	0

Adverse Events

Normal Saline

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Ketamine

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Normal Saline n=9 participants at risk The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 participants at risk The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
General disorders Death	44.4% 4/9 • Number of events 4 • Seven days from enrollment.	20.0% 2/10 • Number of events 2 • Seven days from enrollment.
Cardiac disorders Pericardial effusion	0.00% 0/9 • Seven days from enrollment.	10.0% 1/10 • Number of events 1 • Seven days from enrollment.
Cardiac disorders Ventricular tachycardia	0.00% 0/9 • Seven days from enrollment.	10.0% 1/10 • Number of events 1 • Seven days from enrollment.

Other adverse events

Measure	Normal Saline n=9 participants at risk The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.	Ketamine n=10 participants at risk The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
Cardiac disorders Tachycardia (atrial fibrillation)	0.00% 0/9 • Seven days from enrollment.	30.0% 3/10 • Number of events 3 • Seven days from enrollment.
Nervous system disorders Delirium	0.00% 0/9 • Seven days from enrollment.	10.0% 1/10 • Number of events 1 • Seven days from enrollment.
Gastrointestinal disorders Salivation, excessive	0.00% 0/9 • Seven days from enrollment.	10.0% 1/10 • Number of events 1 • Seven days from enrollment.

Additional Information

Dr. Daniel Talmor

Beth Israel Deaconess Medical Center

Phone: 617-754-2675

Email: dtalmor@bidmc.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place