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Trial Outcomes & Findings for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome (NCT NCT03090620)

NCT ID: NCT03090620

Last Updated: 2021-08-23

Results Overview

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert \& calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

19 participants

Primary outcome timeframe

Baseline, immediately before bolus

Results posted on

2021-08-23

Participant Flow

Participant milestones

Participant milestones
Measure
Physostigmine
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Overall Study
STARTED
9
10
Overall Study
COMPLETED
9
10
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Total
n=19 Participants
Total of all reporting groups
Age, Continuous
13.4 years
STANDARD_DEVIATION 1.4 • n=9 Participants
14.4 years
STANDARD_DEVIATION 1.3 • n=10 Participants
13.9 years
STANDARD_DEVIATION 1.3 • n=19 Participants
Sex: Female, Male
Female
5 Participants
n=9 Participants
7 Participants
n=10 Participants
12 Participants
n=19 Participants
Sex: Female, Male
Male
4 Participants
n=9 Participants
3 Participants
n=10 Participants
7 Participants
n=19 Participants
Race and Ethnicity Not Collected
—
—
0 Participants
Race and Ethnicity were not collected from any participant.
Region of Enrollment
United States
9 participants
n=9 Participants
10 participants
n=10 Participants
19 participants
n=19 Participants
Mean Heart Rate
127 Beats per minute
STANDARD_DEVIATION 18 • n=9 Participants
117 Beats per minute
STANDARD_DEVIATION 10 • n=10 Participants
122 Beats per minute
STANDARD_DEVIATION 14 • n=19 Participants
Mean Temperature
37.3 Celsius
STANDARD_DEVIATION 0.6 • n=9 Participants
37.1 Celsius
STANDARD_DEVIATION 0.5 • n=10 Participants
37.2 Celsius
STANDARD_DEVIATION 0.5 • n=19 Participants
Mean Respiratory Rate
29 Respirations per minute
STANDARD_DEVIATION 7 • n=9 Participants
24 Respirations per minute
STANDARD_DEVIATION 4 • n=10 Participants
27 Respirations per minute
STANDARD_DEVIATION 5 • n=19 Participants
Mean Systolic Blood Pressure
131 mmHg
STANDARD_DEVIATION 12 • n=9 Participants
127 mmHg
STANDARD_DEVIATION 14 • n=10 Participants
129 mmHg
STANDARD_DEVIATION 13 • n=19 Participants
Mean Diastolic Blood Pressure
80 nnHg
STANDARD_DEVIATION 11 • n=9 Participants
88 nnHg
STANDARD_DEVIATION 17 • n=10 Participants
84 nnHg
STANDARD_DEVIATION 14 • n=19 Participants
Mean Oxygen Saturations
96 %Oxygen
STANDARD_DEVIATION 2 • n=9 Participants
97 %Oxygen
STANDARD_DEVIATION 3 • n=10 Participants
96 %Oxygen
STANDARD_DEVIATION 2 • n=19 Participants

PRIMARY outcome

Timeframe: Baseline, immediately before bolus

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert \& calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus
1.5 score on a scale
Interval 1.0 to 2.0
1 score on a scale
Interval 1.0 to 1.5

PRIMARY outcome

Timeframe: Immediately after bolus, up to 10 minutes post-Baseline

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert \& calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Comparison of RASS Score Between Physostigmine and Lorazepam: After Bolus
0 score on a scale
Interval 0.0 to 0.0
1 score on a scale
Interval 1.0 to 2.5

PRIMARY outcome

Timeframe: 4 hours

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert \& calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Comparison of RASS Score Between Physostigmine and Lorazepam: 4 Hours
0 score on a scale
Interval 0.0 to 0.0
0.25 score on a scale
Interval -1.5 to 1.5

PRIMARY outcome

Timeframe: Baseline, immediately before bolus

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: Before Bolus
9 Participants
9 Participants

PRIMARY outcome

Timeframe: Immediately after bolus, up to 10 minutes post-Baseline

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After Bolus
4 Participants
10 Participants

PRIMARY outcome

Timeframe: 4 hours

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 4 Hours
2 Participants
10 Participants

SECONDARY outcome

Timeframe: Up to 4 hours

Evaluation of clinical antimuscarinic symptoms, along with presence of any adverse effects, during the infusion to report tolerability, safety profile, and effectiveness of the infusion. the number of participants exhibiting adverse events will be reported, by type.

Outcome measures

Outcome measures
Measure
Physostigmine
n=9 Participants
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 Participants
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Seizures
0 Participants
0 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Bradycardia
0 Participants
0 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Bronchorrhea
0 Participants
0 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Bronchospasm
0 Participants
0 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Diaphoresis
0 Participants
0 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Intubation
0 Participants
0 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Vomiting
1 Participants
1 Participants
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Oversedation
1 Participants
1 Participants

Adverse Events

Physostigmine

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Lorazepam

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Physostigmine
n=9 participants at risk
Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours. Physostigmine: Administration of physostigmine bolus followed by an infusion
Lorazepam
n=10 participants at risk
Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours. Lorazepam: Administration of lorazepam bolus followed by normal saline infusion
Gastrointestinal disorders
Vomitnig
11.1%
1/9 • Number of events 1 • 4 Hours
10.0%
1/10 • Number of events 1 • 4 Hours
Nervous system disorders
Oversedation
11.1%
1/9 • Number of events 1 • 4 Hours
10.0%
1/10 • Number of events 1 • 4 Hours

Additional Information

Dr. George Sam Wang

UColorado

Phone: 303-724-9967

Results disclosure agreements

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