Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| American Academy of Clinical Toxicology | OTHER |
Not provided
Not provided
Not provided
Overdose of xenobiotics (antihistamines, antipsychotics, or Jimson Weed) with resulting antimuscarinic toxidrome is a common scenario in medical toxicology. The result of antagonism of muscarinic receptors is a constellation of signs and symptoms (toxidrome): mydriasis, decreased sweat, decreased bowel sounds, agitation, delirium, hallucinations, urinary retention, tachycardia, flushed skin and seizures. Two treatment options are physostigmine or benzodiazepines.
Although the antimuscarinic toxidrome occurs commonly, physostigmine has been used sparingly despite evidence of safety and efficacy. To demonstrate the utility and safety of physostigmine, the investigators propose a randomized clinical trial of physostigmine compared to benzodiazepine for antimuscarinic toxicity.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Physostigmine | Experimental | 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. |
|
| Lorazepam | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Physostigmine | Drug | Administration of physostigmine bolus followed by an infusion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of RASS Score Between Physostigmine and Lorazepam: 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. | Baseline, immediately before bolus |
| Comparison of RASS Score Between Physostigmine and Lorazepam: After 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. | Immediately after bolus, up to 10 minutes post-Baseline |
| Comparison of RASS Score Between Physostigmine and Lorazepam: 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. | 4 hours |
| Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome. | 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. | Up to 4 hours |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| George S Wang, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Anschutz Medical Campus, Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Lorazepam |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Comparison of RASS Score Between Physostigmine and Lorazepam: 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. | Posted | Median | Inter-Quartile Range | score on a scale | Baseline, immediately before bolus |
|
4 Hours
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomitnig | Gastrointestinal disorders | Systematic Assessment | Vomiting during treatment |
We had a smaller sample size. All patients in our cohort ingested antihistamines, the majority of which was diphenhydramine. There were no ingestions of other antimuscarinic xenobiotics. Many of the subjects were enrolled during the overnight hours; in addition to the underlying sedation effect of the ingested agent made an assessment of delirium challenging which may have led to more positive delirium scores in both treatment arms. We did not assess efficacy or safety beyond 4 hours.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. George Sam Wang | UColorado | 303-724-9967 | george.wang@childrenscolorado.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 16, 2019 | Jul 28, 2021 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D010830 | Physostigmine |
| D008140 | Lorazepam |
| ID | Term |
|---|---|
| D048448 | Phenylcarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Lorazepam |
| Drug |
Administration of lorazepam bolus followed by normal saline infusion |
|
| Baseline, immediately before bolus |
| Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After 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. | Immediately after bolus, up to 10 minutes post-Baseline |
| Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 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. | 4 hours |
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mean Heart Rate | Mean | Standard Deviation | Beats per minute |
|
| Mean Temperature | Mean | Standard Deviation | Celsius |
|
| Mean Respiratory Rate | Mean | Standard Deviation | Respirations per minute |
|
| Mean Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Mean Diastolic Blood Pressure | Mean | Standard Deviation | nnHg |
|
| Mean Oxygen Saturations | Mean | Standard Deviation | %Oxygen |
|
| OG001 |
| 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 |
|
|
| Primary | Comparison of RASS Score Between Physostigmine and Lorazepam: After 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. | Posted | Median | Inter-Quartile Range | score on a scale | Immediately after bolus, up to 10 minutes post-Baseline |
|
|
|
| Primary | Comparison of RASS Score Between Physostigmine and Lorazepam: 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. | Posted | Median | Inter-Quartile Range | score on a scale | 4 hours |
|
|
|
| Primary | Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 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. | Posted | Count of Participants | Participants | Baseline, immediately before bolus |
|
|
|
| Secondary | Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome. | 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. | Posted | Count of Participants | Participants | Up to 4 hours |
|
|
|
| Primary | Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After 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. | Posted | Count of Participants | Participants | Immediately after bolus, up to 10 minutes post-Baseline |
|
|
|
| Primary | Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 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. | Posted | Count of Participants | Participants | 4 hours |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 2 |
| 9 |
| EG001 | 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 | 0 | 10 | 0 | 10 | 2 | 10 |
| Oversedation | Nervous system disorders | Systematic Assessment | Sleepiness, oversedation |
|
Not provided
Not provided
| D009930 |
| Organic Chemicals |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D001570 | Benzodiazepinones |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| Bronchorrhea |
|
| Bronchospasm |
|
| Diaphoresis |
|
| Intubation |
|
| Vomiting |
|
| Oversedation |
|