Anticholinergic ToxicityPhase 2RIVA-APNCT06399679
Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium
A Phase 2 study testing Rivastigmine in people with Anticholinergic Toxicity, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Antimuscarinic delirium (AMD) is a common and dangerous toxicology condition caused by poisoning by medications and other chemicals that block muscarinic receptors. Physostigmine is effective in reversing AMD but has a short duration of action, and patient commonly experience recurrence of AMD after initial control… Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Anticholinergic Toxicity
- What is being tested?
- Rivastigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2024to Dec 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 10 years of age or older
- Diagnosis of antimuscarinic delirium by history and physical examination, in the opinion of the treating attending toxicologist.
- Treatment with physostigmine according to the local standard of care is planned or has been administered by the treating attending toxicologist and is acceptable to the patient's primary attending physician and surrogate decision maker.
- Antimuscarinic delirium is reasonably controlled after initial physostigmine treatment, as determined by treating toxicologist on bedside physical examination. (Patients may begin the screening and enrollment process prior to physostigmine administration, but will not undergo final initiation of study treatment until after response to physostigmine has been confirmed).
Who cannot join
- Age less than 10 years at time of enrollment
- Surrogate decision maker not available to provide informed consent for enrollment.
- Patient is pregnant or a ward of the state.
- Inability to safely tolerate oral medication, in the judgement of the treating attending physician.
- Evidence of significant risk for serious cardiac or neurologic sequelae of antimuscarinic poisoning:
- Any known or suspected seizure activity prior to enrollment b. QRS duration >100 milliseconds on EKG at enrollment c. Any ventricular dysrhythmia prior to enrollment d. Respiratory failure of any etiology requiring endotracheal intubation e. Any hypotension at enrollment: i. Adults: systolic blood pressure (SBP) <90 mmHg ii. Children ≥10: systolic blood pressure (SBP) <90 mmHg, as per Pediatric Advanced Life Support (PALS) age-based cutoff for children 10 years of age or older3 f. Any administration of sodium bicarbonate, hypertonic saline, vasopressors, inotropes, antiarrhythmic agents, or intravenous lipid emulsion prior to enrollment.
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- Unacceptable risk of serious medical sequelae of antimuscarinic poisoning in the judgment of the treating attending toxicologist.
- Evidence of significant risk of adverse effect of AChE-I:
- a.Bradycardia or risk of AChE-I induced bradycardia at enrollment: i. Adults: heart rate (HR) <80 beats per minute ii. Children: heart rate below the median heart rate for age as proposed by Fleming et al.33:
- 1. Ages 10-12: HR <84 beats per minute 2. Ages 12-15: HR <78 beats per minute 3. Ages 15-18: HR <73 beats per minute b. Known or suspected seizure disorder. c. History of asthma or COPD or wheezing during index presentation d. Known or suspected physical obstruction of intestinal or urogenital tract i. Ileus and/or urinary retention due to antimuscarinic poisoning do not exclude patients from enrollment.
- Known or suspected peptic ulcer disease.
- Any known allergy or intolerance to rivastigmine or other AChEI.
- Failure to achieve reasonable initial control of antimuscarinic delirium after physostigmine administration, as assessed by treating toxicologist on bedside physical examination.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium After Initial Control With Physostigmine (RIVA-AP): a Randomized, Placebo-controlled Trial
Antimuscarinic delirium (AMD) is a common and dangerous toxicology condition caused by poisoning by medications and other chemicals that block muscarinic receptors. Physostigmine is effective in reversing AMD but has a short duration of action, and patient commonly experience recurrence of AMD after initial control with physostigmine.
Recent case reports and small observational studies suggest that rivastigmine, which has a longer duration of action than physostigmine, might be useful in the treatment of AMD. In order to investigate the effectiveness of rivastigmine in preventing recurrence of AMD after initial control with physostigmine, the investigators propose a randomized, placebo-controlled clinical trial of rivastigmine for AMD. The investigators hypothesize that patients treated with rivastigmine after initial control of AMD with physostigmine will experience less recurrence of antimuscarinic delirium than those treated with placebo.
- Conditions
- Anticholinergic Toxicity
- Being tested
- Rivastigmine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivastigmineDrug
Rivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses
PlaceboDrug
Matching oral placebo by mouth once, followed by placebo by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses
| Study group | Role | What they receive |
|---|---|---|
| Rivastigmine | Experimental | Patients in the rivastigmine arm will receive rivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for up to three doses. Receives: Drug: Rivastigmine |
| Placebo | Placebo comparator | Patients in the placebo arm will receive oral placebo by mouth once, followed by oral placebo every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for up to three doses. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of AMD recurrence
Incidence of AMD recurrence, as defined by the development of agitation (Richmond Agitation-Sedation Scale of +1 or higher) and delirium (Confusion Assessment Method for the ICU positive) after initial control of AMD with physostigmine.
Measured: Typically 8-36 hours after randomization
Secondary outcomes (11)
Duration of agitation and delirium
Total duration of time during which patient is experiencing agitation and delirium (defined and assessed as above)
Measured: Typically 8-36 hours after randomization
Total amount of sedatives administered
Total amount of sedatives (antipsychotics, benzodiazepines, dexmedetomidine, propofol, fentanyl, ketamine) administered during the study period.
Measured: Typically 8-36 hours after randomization
Use of sedative infusions
Any use of continuous sedative infusion (dexmedetomidine, benzodiazepine, propofol, fentanyl) during the study period.
Measured: Typically 8-36 hours after randomization
Use of physical restraints
Any use of physical restraints during the study period
Measured: Typically 8-36 hours after randomization
Disposition
Disposition to ICU, stepdown/intermediate care unit, or floor level of care
Measured: Typically 8-36 hours after randomization
Time to medical clearance
Time from presentation to medical clearance by the toxicology consult service
Measured: Typically 8-36 hours after randomization
Oversedation
Incidence of oversedation, defined as RASS lower than -2
Measured: Typically 8-36 hours after randomization
Intubation
Incidence of intubation and mechanical ventilation during the study period
Measured: Typically 8-36 hours after randomization
Seizure
Incidence of epileptic seizure during the study period
Measured: Typically 8-36 hours after randomization
Gastrointestinal upset
Incidence of clinically significant gastrointestinal upset during the study period
Measured: Typically 8-36 hours after randomization
Bradycardia
Incidence of any bradycardia (as defined using age-based heart rate cutoffs) during the study period
Measured: Typically 8-36 hours after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start4 Nov 2024
- Primary completionNov 2028 (estimated)
- Study completionDec 2028 (estimated)
Why it stopped: Physostigmine (standard of care treatment under this protocol) became unavailable at the study site June 1st 2026, requiring suspension of the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anticholinergic ToxicityStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- American Academy of Clinical Toxicology
- Responsible party
- Principal investigator, Kevin Baumgartner, Washington University School of Medicine
- Investigators
- Kevin Baumgartner, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06399679
- Sponsor's protocol ID
- 202403052
- Acronym
- RIVA-AP
- Status last verified
- Jun 2026
- First submitted
- 30 Apr 2024
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium After Initial Control With Physostigmine (RIVA-AP): a Randomized, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT06399679
- Acronym / sponsor ID
- RIVA-AP / 202403052
- Conditions
- Anticholinergic Toxicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Physostigmine (standard of care treatment under this protocol) became unavailable at the study site June 1st 2026, requiring suspension of the study.
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- American Academy of Clinical Toxicology
- Study start
- 4 Nov 2024 (actual)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 6 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antimuscarinic delirium (AMD) is a common and dangerous toxicology condition caused by poisoning by medications and other chemicals that block muscarinic receptors. Physostigmine is effective in reversing AMD but has a short duration of action, and patient commonly experience recurrence of AMD after initial control with physostigmine.
Recent case reports and small observational studies suggest that rivastigmine, which has a longer duration of action than physostigmine, might be useful in the treatment of AMD. In order to investigate the effectiveness of rivastigmine in preventing recurrence of AMD after initial control with physostigmine, the investigators propose a randomized, placebo-controlled clinical trial of rivastigmine for AMD. The investigators hypothesize that patients treated with rivastigmine after initial control of AMD with physostigmine will experience less recurrence of antimuscarinic delirium than those treated with placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivastigmine | Experimental | Drug: RivastigminePatients in the rivastigmine arm will receive rivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for up to three doses. |
| Placebo | Placebo comparator | Drug: PlaceboPatients in the placebo arm will receive oral placebo by mouth once, followed by oral placebo every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for up to three doses. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 10 years of age or older
- Diagnosis of antimuscarinic delirium by history and physical examination, in the opinion of the treating attending toxicologist.
- Treatment with physostigmine according to the local standard of care is planned or has been administered by the treating attending toxicologist and is acceptable to the patient's primary attending physician and surrogate decision maker.
- Antimuscarinic delirium is reasonably controlled after initial physostigmine treatment, as determined by treating toxicologist on bedside physical examination. (Patients may begin the screening and enrollment process prior to physostigmine administration, but will not undergo final initiation of study treatment until after response to physostigmine has been confirmed).
Key exclusion criteria (13 listed)
- Age less than 10 years at time of enrollment
- Surrogate decision maker not available to provide informed consent for enrollment.
- Patient is pregnant or a ward of the state.
- Inability to safely tolerate oral medication, in the judgement of the treating attending physician.
- Evidence of significant risk for serious cardiac or neurologic sequelae of antimuscarinic poisoning:
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 |
|---|---|---|
| RivastigmineRivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses | Drug | Rivastigmine |
| PlaceboMatching oral placebo by mouth once, followed by placebo by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses | Drug | Placebo |
Primary outcome
Incidence of AMD recurrence
Time frame: Typically 8-36 hours after randomization
Incidence of AMD recurrence, as defined by the development of agitation (Richmond Agitation-Sedation Scale of +1 or higher) and delirium (Confusion Assessment Method for the ICU positive) after initial control of AMD with physostigmine.
11 secondary outcomes
Duration of agitation and delirium
Time frame: Typically 8-36 hours after randomization
Total amount of sedatives administered
Time frame: Typically 8-36 hours after randomization
Use of sedative infusions
Time frame: Typically 8-36 hours after randomization
Use of physical restraints
Time frame: Typically 8-36 hours after randomization
Disposition
Time frame: Typically 8-36 hours after randomization
Time to medical clearance
Time frame: Typically 8-36 hours after randomization
Oversedation
Time frame: Typically 8-36 hours after randomization
Intubation
Time frame: Typically 8-36 hours after randomization
Seizure
Time frame: Typically 8-36 hours after randomization
Gastrointestinal upset
Time frame: Typically 8-36 hours after randomization
Bradycardia
Time frame: Typically 8-36 hours after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Individual participant dataSharing planned: Undecided
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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.
Kevin Baumgartner, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rivastigmine in people with Anticholinergic Toxicity, run by Washington University School of Medicine 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 13 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: paused, as of the sponsor's last update on 4 Jun 2026. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Incidence of AMD recurrence (time frame: Typically 8-36 hours after randomization). 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 4 Jun 2026.