Rivastigmine for Delirium
(RIVA-AP Trial)
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Washington University School of Medicine
Must be taking: Physostigmine
Must not be taking: Sodium bicarbonate, Vasopressors
Disqualifiers: Pregnancy, Seizure disorder, Asthma, others
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this 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.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Eligibility Criteria
This trial is for patients who have experienced antimuscarinic delirium (AMD), a type of confusion and agitation caused by certain medications or poisons. Participants must have had their AMD initially controlled with physostigmine but are at risk of its recurrence.Inclusion Criteria
I am 10 years old or older.
I have been diagnosed with delirium caused by antimuscarinic drugs.
My confusion from antimuscarinic delirium is under control after treatment.
+1 more
Exclusion Criteria
I cannot safely take pills, as determined by my doctor.
I am at high risk for serious heart or brain problems from antimuscarinic poisoning.
I am at high risk for side effects from AChE inhibitors.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive either rivastigmine or placebo to prevent recurrence of antimuscarinic delirium after initial control with physostigmine
8-36 hours
Continuous monitoring during treatment
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 week
Participant Groups
The study tests if rivastigmine, which lasts longer than physostigmine, can prevent the return of AMD symptoms after initial treatment. Patients will be randomly assigned to receive either rivastigmine or a placebo in this controlled trial.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: RivastigmineExperimental Treatment1 Intervention
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.
Group II: PlaceboPlacebo Group1 Intervention
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.
Rivastigmine is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Exelon for:
- Alzheimer's Disease
- Parkinson's Disease Dementia
🇺🇸 Approved in United States as Exelon for:
- Alzheimer's Disease
- Parkinson's Disease Dementia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
American Academy of Clinical ToxicologyCollaborator
American Academy of Clinical ToxicologyCollaborator
References
A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer's disease. [2022]The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713; Exelon, in patients with mild to moderately severe Alzheimer's disease was evaluated in a 26-week open-label extension of a 26-week, double-blind, placebo-controlled study. By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had significantly better cognitive function than patients originally treated with placebo.
Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers. [2018]To assess the bioequivalence of generic formulation of rivastigmine (test) and Exelon (reference).
A review of rivastigmine: a reversible cholinesterase inhibitor. [2022]Rivastigmine tartrate is a reversible cholinesterase inhibitor indicated for the symptomatic treatment of mild to moderate dementia. It was approved by the US Food and Drug Administration for the treatment of Alzheimer's disease (AD) on April 21, 2000.
Impact of rivastigmine patch and capsules on activities of daily living in Alzheimer's disease. [2015]Rivastigmine patches provide similar efficacy to rivastigmine capsules with a lower incidence of gastrointestinal side effects in patients with probable Alzheimer's disease (AD).
Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe Alzheimer's disease: a meta-analysis. [2018]To evaluate the long-term effectiveness of rivastigmine patch or capsule on mild to severe Alzheimer's disease (AD).
Rivastigmine transdermal patch 13.3 mg/24 h: a review of its use in the management of mild to moderate Alzheimer's dementia. [2021]Rivastigmine is unique among cholinesterase inhibitors commonly used in the treatment of mild to moderate Alzheimer's disease (AD) in that it is available as a transdermal patch formulation (Exelon(®) patch, Rivastach(®) patch, Prometax(®) patch). The patch is applied once daily and, in the EU (and US), is available in three sizes: 5, 10 and 15 cm(2) (releasing 4.6, 9.5 and 13.3 mg rivastigmine/24 h, respectively). In the phase III OPTIMA trial, patients with mild to moderate AD who experienced functional and cognitive decline on the 10 cm(2) patch-the recommended maintenance dose-gained additional benefit when their dose was increased to the 15 cm(2) patch. For example, 15 cm(2) patch recipients showed significantly less functional and cognitive decline than 10 cm(2) patch recipients after 24 weeks of double-blind treatment. Patients receiving the 15 cm(2) patch also showed significantly less functional, but not cognitive, decline than those receiving the 10 cm(2) patch after 48 weeks of double-blind treatment; as such, OPTIMA only met one of its two co-primary endpoints. The 15 cm(2) patch was generally well tolerated; although more 15 cm(2) than 10 cm(2) patch recipients reported adverse events (e.g. nausea and vomiting), fewer 15 cm(2) than 10 cm(2) patch recipients discontinued treatment due to adverse events. By further slowing functional deterioration without markedly compromising tolerability, increasing the transdermal rivastigmine dose to the 15 cm(2) patch has a favourable benefit-risk profile-and therefore represents a valid option-in the treatment of patients with mild to moderate AD who have previously experienced functional and cognitive decline while receiving the 10 cm(2) patch.
Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects. [2022]Rivastigmine is a reversible cholinesterase inhibitor indicated for the treatment of all stages of Alzheimer's disease (AD). Transdermal patch formulation allows smooth and continuous drug delivery. Its tolerability, efficacy and convenience of use increase treatment compliance. This study was designed to evaluate the bioavailability and to assess the bioequivalence of two rivastigmine transdermal patches at steady state (RIV-TDS Test Product versus Exelon Marketed Reference Product), with a release rate of 13.3 mg/24 h, after multiple patch applications. As secondary objectives, safety, patch adhesion and skin irritation were evaluated.
A fatal outcome after unintentional overdosing of rivastigmine patches. [2019]Rivastigmine is an acetylcholine esterase inhibitor used in the treatment of dementia. Patches with rivastigmine for transdermal delivery have been used to increase compliance and to reduce side effects.