Anticholinergics ToxicityPhase 4TAATNCT03090620
Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome
A Phase 4 study testing Physostigmine and Lorazepam in people with Anticholinergics Toxicity, run by University of Colorado, Denver at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 10 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Anticholinergics Toxicity
- What is being tested?
- Physostigmine and Lorazepam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Mar 2017to 31 Aug 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age >=10 and < 18 years
- Present to the Emergency Department or Intensive Care Unit for an antimuscarinic toxidrome from either a pharmaceutical agent such as antihistamine overdose, or natural toxins or products such as Datura stramonium
- Antimuscarinic toxidrome will be defined with at least one central nervous system agitation effect (agitation, delirium, visual hallucinations, mumbling incomprehensible speech), and at least 2 peripheral nervous system adverse effect (mydriasis, dry mucus membranes, dry axillae, tachycardia, decreased bowel sounds).
- Patients will also be required to have a RASS score of +2 to +4 on initial assessment.
Who cannot join
- History of seizures or seizure during acute clinical course
- History of asthma or wheezing during clinical course Bradycardia (Heart Rate <60)
- Concomitant use of atropine or choline ester or depolarizing neuromuscular blocker during present illness and hospital course
- Diabetes gangrene, known intestinal obstruction or urogenital tract, vagotonic state
- QRS interval > 120 ms on electrocardiogram
- Known to be pregnant at the time of enrollment
- Known ward of the state
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Campus, Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
Official title: A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome
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.
- Conditions
- Anticholinergics Toxicity
- Being tested
- Physostigmine, Lorazepam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhysostigmineDrug
Administration of physostigmine bolus followed by an infusion
LorazepamDrug
Administration of lorazepam bolus followed by normal saline infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Physostigmine |
| 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. Receives: Drug: Lorazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 4 hours
Secondary outcomes (1)
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.
Measured: Up to 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start30 Mar 2017
- Primary completion31 Jul 2020
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anticholinergics ToxicityStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- American Academy of Clinical Toxicology
- Responsible party
- Sponsor
- Investigators
- George S Wang, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090620
- Sponsor's protocol ID
- 16-1730
- Acronym
- TAAT
- Status last verified
- Jul 2021
- First submitted
- 10 Mar 2017
- Last updated
- 23 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome
- ClinicalTrials.gov ID
- NCT03090620
- Acronym / sponsor ID
- TAAT / 16-1730
- Conditions
- Anticholinergics Toxicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- American Academy of Clinical Toxicology
- Study start
- 30 Mar 2017 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 27 Mar 2017 (actual)
- Results
- Posted 23 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Physostigmine | Experimental | Drug: PhysostigminePhysostigmine 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 | Drug: LorazepamLorazepam 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. |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Age >=10 and < 18 years
- Present to the Emergency Department or Intensive Care Unit for an antimuscarinic toxidrome from either a pharmaceutical agent such as antihistamine overdose, or natural toxins or products such as Datura stramonium
- Antimuscarinic toxidrome will be defined with at least one central nervous system agitation effect (agitation, delirium, visual hallucinations, mumbling incomprehensible speech), and at least 2 peripheral nervous system adverse effect (mydriasis, dry mucus membranes, dry axillae, tachycardia, decreased bowel sounds).
- Patients will also be required to have a RASS score of +2 to +4 on initial assessment.
Key exclusion criteria (7 listed)
- History of seizures or seizure during acute clinical course
- History of asthma or wheezing during clinical course Bradycardia (Heart Rate <60)
- Concomitant use of atropine or choline ester or depolarizing neuromuscular blocker during present illness and hospital course
- Diabetes gangrene, known intestinal obstruction or urogenital tract, vagotonic state
- QRS interval > 120 ms on electrocardiogram
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhysostigmineAdministration of physostigmine bolus followed by an infusion | Drug | Physostigmine |
| LorazepamAdministration of lorazepam bolus followed by normal saline infusion | Drug | Lorazepam |
Primary outcome
Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus
Time frame: 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.
Comparison of RASS Score Between Physostigmine and Lorazepam: After Bolus
Time frame: 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.
Comparison of RASS Score Between Physostigmine and Lorazepam: 4 Hours
Time frame: 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.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: Before Bolus
Time frame: 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.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After Bolus
Time frame: 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.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 4 Hours
Time frame: 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.
1 secondary outcome
Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.
Time frame: Up to 4 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Anticholinergics Toxicity
RecruitingPhase 2
Rivastigmine for Antimuscarinic Delirium
Anticholinergic Toxicity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George S Wang, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Physostigmine and Lorazepam in people with Anticholinergics Toxicity, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus (time frame: Baseline, immediately before bolus). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2021.