Anticholinergic DeliriumPhase 4NCT07545382
Rivastigmine as an Antidote for Clozapine-induced Central Nervous System Depression and Delirium
A Phase 4 study testing Rivastigmine in people with Anticholinergic Delirium and Clozapine Poisoning, run by Alexandria University at 1 site in Egypt.
Trial summary
This study aims to evaluate the clinical efficacy and safety of rivastigmine in reversing the full spectrum of anticholinergic delirium including hypoactive delirium which is presented with CNS depression and hyperactive or agitated delirium. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anticholinergic Delirium, Clozapine Poisoning, Antipsychotic Toxicity
- What is being tested?
- Rivastigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 8 Dec 2025to 15 Apr 2026
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Exposure: acute exposure to anticholinergic agents (e.g., clozapine, tricyclic antidepressants).
- Clinical Presentation: Presence of anticholinergic delirium either hyperactive/agitated or hypoactive/CNS depression/coma).
Who cannot join
- Non-Toxic Delirium: Delirium of multifactorial origin or other medical causes (e.g., sepsis, hepatic encephalopathy, alcohol withdrawal, or metabolic disturbances).
- Cardiac Contraindications: Baseline bradycardia, Atrioventricular (AV) block, or significant QTc prolongation.
- Patients who experienced pulmonary aspiration as a complication of overdose, necessitating endotracheal intubation and mechanical ventilation
- Severe Organ Impairment: Known severe renal or hepatic impairment.
- Neurological Conditions: History of pre-existing seizure disorders or epilepsy.
- Respiratory Conditions: Severe asthma or Chronic Obstructive Pulmonary Disease (COPD) due to the risk of bronchoconstriction.
Show all 9Show fewer
- Obstructions: Mechanical bowel obstruction or urinary tract obstruction.
- Hypersensitivity: Known history of hypersensitivity to rivastigmine or other carbamates.
- Pregnancy/Lactation: Pregnant or lactating women.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Poison Control Center (PCC), Alexandria University Main Hospital
Alexandria, 21131
About this study
Official title: Efficacy of Rivastigmine in the Management of Toxic Anticholinergic Delirium: A Prospective Study at Alexandria Poison Center
This study aims to evaluate the clinical efficacy and safety of rivastigmine in reversing the full spectrum of anticholinergic delirium including hypoactive delirium which is presented with CNS depression and hyperactive or agitated delirium.
The study was conducted on 100 patients at the Poison Control Center of Alexandria University Main Hospital. The primary objective is to assess the effectiveness of rivastigmine in restoring consciousness and improving cognitive function in patients presenting with delirium and depressed mental status using GCS and RASS score.
Read the detailed description
This prospective clinical study assess the efficacy of rivastigmine in reversing the full spectrum of anticholinergic delirium. The study encompasses both hyperactive (agitated) and hypoactive (depressed mental status/CNS depression) presentations, with a specific focus on the hypoactive variant. While anticholinergic toxicity is traditionally associated with agitation, this research highlights its role in causing hypoactive delirium and assesses how rivastigmine facilitates the recovery of consciousness and cognitive function.
Participants:
The study includes 100 patients (aged ≥18 years) with Anticholinergic delirium-induced by exposure to drugs with anticholinergic properties-manifests either as agitated delirium (characterized by confusion, agitation, disorientation, and hallucinations) or hypoactive delirium (characterized by CNS depression). Patient status was assessed using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS) upon admission to the Poison Control Center of Alexandria University Main Hospital (AUMH).
Intervention Protocol:
Administration: An initial enteral dose of 6 mg is administered orally or by nasogastric tube. Transdermal patch was administered when nasogastric route was non-feasible.
Dosing: Additional 6 mg doses are administered every 2 hours until achieving GCS 15 /RASS 0
Assessment \& Resolution:
Awareness, cognition, consciousness, and the level of agitation or sedation were evaluated using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS). These assessments were performed at baseline, 2 hours, and 6 hours for both the oral and transdermal groups, and at 12 hours exclusively for the transdermal group. Clinical success was defined as achieving a GCS score of 15 and a RASS score of 0.
- Conditions
- Anticholinergic Delirium, Clozapine Poisoning, Antipsychotic Toxicity, CNS Depression, Hypoactive Delirium, Tricyclic Antidepressant Poisoning
- Being tested
- Rivastigmine
- Keywords
- Rivastigmine, Clozapine, Quetiapine, Carbamazepine, Procyclidine, Cyproheptadine, Acetylcholinesterase Inhibitors, CNS depression, Hypoactive dilirium, Anticholinergic delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivastigmineDrug
Initial Dose: A starting dose of 6 mg is administered either orally or via a Nasogastric Tube (NGT) for patients with impaired swallowing or depressed consciousness.
Titration: Additional 6 mg doses are repeated every 2 hours based on clinical need until the resolution of delirium.
Alternative Route: Transdermal patches (9.5 mg/24h) are applied in cases where enteral administration is not feasible or based on clinical judgment.
| Study group | Role | What they receive |
|---|---|---|
| Rivastigmine Treatment Group | Experimental | A total of 100 patients presenting with anticholinergic delirium (including both hyperactive and hypoactive variants) were enrolled. Each participant received rivastigmine according to the established clinical titration protocol. Receives: Drug: Rivastigmine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glasgow Coma Scale (GCS) Score.
The Glasgow Coma Scale (GCS) is a clinical scale used to assess a patient's level of consciousness. The total score was recorded for all participants at baseline and subsequent intervals to evaluate the clinical response to rivastigmine. The GCS score ranges from a minimum of 3 to a maximum of 15, where higher scores indicate a better neurological outcome (improved consciousness). For the oral/NGT group, assessments were performed 2 hours after the initial dose and after each supplemental dose. For the transdermal group, monitoring included a 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a GCS score of 15 and a RASS score of 0.
Measured: Baseline (0 hour), 2 hours post-administration (all patients), 6-8 hours, and 12 hours (transdermal group). For patients receiving additional oral/NGT doses, assessments were repeated 2 hours after each supplemental dose up to 6 hours after resolution.
Change in Richmond Agitation-Sedation Scale (RASS) Score
The Richmond Agitation-Sedation Scale (RASS) is used to evaluate the clinical response to rivastigmine. The RASS is a 10-point scale ranging from a minimum value of -5 (denoting unarousable/deep sedation) to a maximum value of +4 (denoting combative/extreme agitation). A score of 0 represents an alert and calm state, which indicates the best clinical outcome for this study. Scores were recorded for all participants at baseline and 2 hours to evaluate the initial response. For the oral/NGT group, additional assessments were performed 2 hours after each supplemental dose. For the transdermal group, monitoring focused on the 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a RASS score of 0 and a GCS score of 15.
Measured: Baseline, 2h (all), 6-8h & 12h (patch group), and up to 6h post-resolution (both groups)
Secondary outcomes (4)
Post-Resolution Clinical Stability and Safety Profile.
Monitoring for potential adverse effects related to rivastigmine, including cardiac complications (e.g., bradycardia, arrhythmias) and cholinergic side effects (e.g., excessive secretions, vomiting). Safety is further assessed by the absence of relapse during a mandatory 6-hour observation period following the resolution of delirium and CNS depression. Patients are deemed clinically stable if they remain symptom-free throughout this period prior to discharge.
Measured: From initial administration up to 6 hours post-resolution of delirium.
Time to Clinical Resolution.
The duration (measured in hours) elapsed from the initial dose of rivastigmine until the patient achieves clinical resolution, defined as reaching a Glasgow Coma Scale (GCS) score of 15 and a Richmond Agitation-Sedation Scale (RASS) score of 0.
Measured: From the time of initial administration until the achievement of clinical resolution.
Resolution of Peripheral Antimuscarinic Features.
Monitoring the normalization of heart rate and the resolution of urinary retention (without the requirement for catheterization) in patients presenting with these features at baseline.
Measured: From initial administration up to the point of CNS manifestation resolution (variable, typically within 2-12 hours).
The requirement for Additional Interventions
The percentage of patients requiring rescue therapy or escalation of care after receiving rivastigmine. This includes the need for benzodiazepines for sedation, the use of physical restraints, or clinical escalation to endotracheal intubation and intensive care unit (ICU) admission.
Measured: From Initiation of Rivastigmine Treatment Until 6 Hours After Recovery of Consciousness
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2026
- Study start8 Dec 2025
- Primary completion15 Apr 2026
- Study completion15 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anticholinergic DeliriumStudies of the same condition, open and under way.
- More trials run by Alexandria UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm, open-label prospective study involving 100 patients who met the inclusion criteria for toxic anticholinergic delirium. All enrolled participants received the intervention (rivastigmine) following a standardized titration protocol. The study uniquely focuses on the reversal of CNS depression and hypoactive delirium, in addition to agitated states. Clinical response and level of arousal were quantitatively monitored using the Glasgow Coma Scale (GCS) to assess the degree of consciousness and the Richmond Agitation-Sedation Scale (RASS) to evaluate the degrees of sedation and agitation, ensuring a comprehensive assessment of the drug's efficacy across the full spectrum of delirium.
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, shimaa Gaber, Alexandria University
- Investigators
- Naima A Sherif, Professor of Forensic Medicine, Study chair, University of AlexandriaRagaa T Darwish, Professor of Forensic Medicine, Study chair, University of AlexandriaSahar Y Issa, Assoc Prof Forensic Med, Study chair, University of Alexandria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07545382
- Sponsor's protocol ID
- 0202283
- Status last verified
- Sep 2026
- First submitted
- 15 Apr 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The individual patient data are part of a PHD's thesis and are currently protected by institutional policies at Alexandria University. The data may be available upon reasonable request from the principal investigator after the final publication of the study results and in accordance with the hospital's ethical committee guidelines."
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Rivastigmine in the Management of Toxic Anticholinergic Delirium: A Prospective Study at Alexandria Poison Center
- ClinicalTrials.gov ID
- NCT07545382
- Acronym / sponsor ID
- 0202283
- Conditions
- Anticholinergic Delirium, Clozapine Poisoning, Antipsychotic Toxicity, CNS Depression, Hypoactive Delirium, Tricyclic Antidepressant Poisoning
- Keywords
- Rivastigmine, Clozapine, Quetiapine, Carbamazepine, Procyclidine, Cyproheptadine, Acetylcholinesterase Inhibitors, CNS depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Study start
- 8 Dec 2025 (actual)
- Primary completion
- 15 Apr 2026 (actual)
- Study completion
- 15 Apr 2026 (actual)
- First posted
- 22 Apr 2026 (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.
This study aims to evaluate the clinical efficacy and safety of rivastigmine in reversing the full spectrum of anticholinergic delirium including hypoactive delirium which is presented with CNS depression and hyperactive or agitated delirium.
The study was conducted on 100 patients at the Poison Control Center of Alexandria University Main Hospital. The primary objective is to assess the effectiveness of rivastigmine in restoring consciousness and improving cognitive function in patients presenting with delirium and depressed mental status using GCS and RASS score.
Detailed description
This prospective clinical study assess the efficacy of rivastigmine in reversing the full spectrum of anticholinergic delirium. The study encompasses both hyperactive (agitated) and hypoactive (depressed mental status/CNS depression) presentations, with a specific focus on the hypoactive variant. While anticholinergic toxicity is traditionally associated with agitation, this research highlights its role in causing hypoactive delirium and assesses how rivastigmine facilitates the recovery of consciousness and cognitive function.
Participants:
The study includes 100 patients (aged ≥18 years) with Anticholinergic delirium-induced by exposure to drugs with anticholinergic properties-manifests either as agitated delirium (characterized by confusion, agitation, disorientation, and hallucinations) or hypoactive delirium (characterized by CNS depression). Patient status was assessed using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS) upon admission to the Poison Control Center of Alexandria University Main Hospital (AUMH).
Intervention Protocol:
Administration: An initial enteral dose of 6 mg is administered orally or by nasogastric tube. Transdermal patch was administered when nasogastric route was non-feasible.
Dosing: Additional 6 mg doses are administered every 2 hours until achieving GCS 15 /RASS 0
Assessment \& Resolution:
Awareness, cognition, consciousness, and the level of agitation or sedation were evaluated using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS). These assessments were performed at baseline, 2 hours, and 6 hours for both the oral and transdermal groups, and at 12 hours exclusively for the transdermal group. Clinical success was defined as achieving a GCS score of 15 and a RASS score of 0.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm, open-label prospective study involving 100 patients who met the inclusion criteria for toxic anticholinergic delirium. All enrolled participants received the intervention (rivastigmine) following a standardized titration protocol. The study uniquely focuses on the reversal of CNS depression and hypoactive delirium, in addition to agitated states. Clinical response and level of arousal were quantitatively monitored using the Glasgow Coma Scale (GCS) to assess the degree of consciousness and the Richmond Agitation-Sedation Scale (RASS) to evaluate the degrees of sedation and agitation, ensuring a comprehensive assessment of the drug's efficacy across the full spectrum of delirium.
| Arm | Type | Receives |
|---|---|---|
| Rivastigmine Treatment Group | Experimental | Drug: RivastigmineA total of 100 patients presenting with anticholinergic delirium (including both hyperactive and hypoactive variants) were enrolled. Each participant received rivastigmine according to the established clinical titration protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Exposure: acute exposure to anticholinergic agents (e.g., clozapine, tricyclic antidepressants).
- Clinical Presentation: Presence of anticholinergic delirium either hyperactive/agitated or hypoactive/CNS depression/coma).
Key exclusion criteria (9 listed)
- Non-Toxic Delirium: Delirium of multifactorial origin or other medical causes (e.g., sepsis, hepatic encephalopathy, alcohol withdrawal, or metabolic disturbances).
- Cardiac Contraindications: Baseline bradycardia, Atrioventricular (AV) block, or significant QTc prolongation.
- Patients who experienced pulmonary aspiration as a complication of overdose, necessitating endotracheal intubation and mechanical ventilation
- Severe Organ Impairment: Known severe renal or hepatic impairment.
- Neurological Conditions: History of pre-existing seizure disorders or epilepsy.
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 |
|---|---|---|
| RivastigmineInitial Dose: A starting dose of 6 mg is administered either orally or via a Nasogastric Tube (NGT) for patients with impaired swallowing or depressed consciousness. Titration: Additional 6 mg doses are repeated every 2 hours based on clinical need until the resolution of delirium. Alternative Route: Transdermal patches (9.5 mg/24h) are applied in cases where enteral administration is not feasible or based on clinical judgment. | Drug | Rivastigmine Treatment Group |
Primary outcome
Change in Glasgow Coma Scale (GCS) Score.
Time frame: Baseline (0 hour), 2 hours post-administration (all patients), 6-8 hours, and 12 hours (transdermal group). For patients receiving additional oral/NGT doses, assessments were repeated 2 hours after each supplemental dose up to 6 hours after resolution.
The Glasgow Coma Scale (GCS) is a clinical scale used to assess a patient's level of consciousness. The total score was recorded for all participants at baseline and subsequent intervals to evaluate the clinical response to rivastigmine. The GCS score ranges from a minimum of 3 to a maximum of 15, where higher scores indicate a better neurological outcome (improved consciousness). For the oral/NGT group, assessments were performed 2 hours after the initial dose and after each supplemental dose. For the transdermal group, monitoring included a 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a GCS score of 15 and a RASS score of 0.
Change in Richmond Agitation-Sedation Scale (RASS) Score
Time frame: Baseline, 2h (all), 6-8h & 12h (patch group), and up to 6h post-resolution (both groups)
The Richmond Agitation-Sedation Scale (RASS) is used to evaluate the clinical response to rivastigmine. The RASS is a 10-point scale ranging from a minimum value of -5 (denoting unarousable/deep sedation) to a maximum value of +4 (denoting combative/extreme agitation). A score of 0 represents an alert and calm state, which indicates the best clinical outcome for this study. Scores were recorded for all participants at baseline and 2 hours to evaluate the initial response. For the oral/NGT group, additional assessments were performed 2 hours after each supplemental dose. For the transdermal group, monitoring focused on the 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a RASS score of 0 and a GCS score of 15.
4 secondary outcomes
Post-Resolution Clinical Stability and Safety Profile.
Time frame: From initial administration up to 6 hours post-resolution of delirium.
Time to Clinical Resolution.
Time frame: From the time of initial administration until the achievement of clinical resolution.
Resolution of Peripheral Antimuscarinic Features.
Time frame: From initial administration up to the point of CNS manifestation resolution (variable, typically within 2-12 hours).
The requirement for Additional Interventions
Time frame: From Initiation of Rivastigmine Treatment Until 6 Hours After Recovery of Consciousness
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Individual participant dataSharing planned: No. The individual patient data are part of a PHD's thesis and are currently protected by institutional policies at Alexandria University. The data may be available upon reasonable request from the principal investigator after the final publication of the study results and in accordance with the hospital's ethical committee guidelines."
Related trials for Anticholinergic Delirium
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.
Naima A Sherif, Professor of Forensic Medicine study chair
University of Alexandria
Ragaa T Darwish, Professor of Forensic Medicine study chair
University of Alexandria
Sahar Y Issa, Assoc Prof Forensic Med study chair
University of Alexandria
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 Rivastigmine in people with Anticholinergic Delirium and Clozapine Poisoning, run by Alexandria University at 1 site in Egypt.
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 2 inclusion and 9 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 21 Sep 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 Egypt. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Glasgow Coma Scale (GCS) Score. (time frame: Baseline (0 hour), 2 hours post-administration (all patients), 6-8 hours, and 12 hours (transdermal group). For patients receiving additional oral/NGT doses, assessments were repeated 2 hours after each supplemental dose up to 6 hours after resolution.). The study lists 2 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 21 Sep 2026.