Rivastigmine for Delirium

(RIVA-AM Trial)

Not currently recruiting at 1 trial location

Overseen By Kevin Baumgartner, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Sodium bicarbonate, Vasopressors

Disqualifiers: Seizure disorder, Asthma, COPD, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8-36 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests rivastigmine to determine its effectiveness in treating antimuscarinic delirium, a type of confusion and agitation caused by certain poisons. Since the usual treatment, physostigmine, is difficult to obtain, researchers aim to assess whether rivastigmine can serve as a suitable alternative. Participants will receive either rivastigmine or a placebo (a pill with no active drug) to evaluate which better alleviates symptoms. This trial suits individuals diagnosed with antimuscarinic delirium who experience significant confusion and agitation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that rivastigmine is likely to be safe for humans?

Research has shown that rivastigmine is generally safe for use. In other studies, some patients taking rivastigmine experienced common side effects such as nausea, vomiting, and dizziness, which were usually mild. Rivastigmine has also been used in patients with Alzheimer's disease, providing insights into its safety. However, using rivastigmine for antimuscarinic delirium (AMD) remains under investigation, so more research is needed to fully understand its safety and effectiveness for this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for delirium?

Rivastigmine is unique because it targets delirium through a mechanism that is different from standard treatments like antipsychotics and benzodiazepines. Most current options focus on calming symptoms, but Rivastigmine works by enhancing communication between nerve cells in the brain, potentially addressing the root cause of delirium. Researchers are excited about Rivastigmine because it offers a possibility for more rapid symptom control and may reduce the need for sedative medications, which often come with side effects. This approach could lead to better outcomes for patients experiencing delirium, which is a common and challenging condition in hospitals.

What evidence suggests that rivastigmine might be an effective treatment for antimuscarinic delirium?

Research has shown that rivastigmine, a type of medication, can improve thinking and reduce restlessness in people with mild to moderate Alzheimer’s disease. This suggests potential benefits for antimuscarinic delirium (AMD), a condition marked by confusion and agitation. Some small studies and reports have indicated that rivastigmine could alleviate AMD symptoms. In this trial, participants in the rivastigmine arm will receive rivastigmine to assess its effectiveness for ongoing delirium or agitation. Although it hasn't been directly compared to the usual treatment, physostigmine, rivastigmine's ability to enhance cognition and calm agitation makes it a promising option for treating AMD. ^{5 6 7 8 9}

Who Is on the Research Team?

Kevin Baumgartner, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals experiencing antimuscarinic delirium, a type of confusion and agitation due to certain medication or chemical poisoning. Details on who can join are not provided, but typically participants must meet specific health criteria.

Inclusion Criteria

Diagnosis of antimuscarinic delirium by history and physical examination, in the opinion of the treating attending toxicologist

I am at least 10 years old.

I am experiencing significant agitation and confusion that could improve with specific treatment.

Exclusion Criteria

I am under 10 years old.

Patient is pregnant or a ward of the state

Inability to safely tolerate oral medication, in the judgement of the treating attending physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive rivastigmine or placebo for antimuscarinic delirium, with doses administered as needed for ongoing delirium or agitation

8-36 hours

Continuous monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of agitation and delirium

1 week

Regular assessments every 2 hours until sustained recovery

What Are the Treatments Tested in This Trial?

Interventions

• Rivastigmine

Trial Overview

The study tests if rivastigmine helps treat antimuscarinic delirium faster than a placebo. Participants will be randomly assigned to receive either rivastigmine or an inactive substance (placebo) in this controlled trial.

How Is the Trial Designed?

Group I: Rivastigmine Experimental Treatment 1 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: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

American Academy of Clinical Toxicology

Collaborator

Trials

3

Recruited

100+

American Academy of Clinical Toxicology

Collaborator

Trials

3

Recruited

100+

Published Research Related to This Trial

The study demonstrated that the new rivastigmine transdermal patch (RIV-TDS) is bioequivalent to the marketed Exelon patch, meaning they deliver the same amount of the drug into the bloodstream, which is important for consistent treatment of Alzheimer's disease.

RIV-TDS showed better skin adhesion and tolerability compared to the reference product, suggesting it may enhance patient compliance and comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects. Morte, A., Vaqué, A., Iniesta, M., et al.[2022]

In a 52-week study involving patients with mild to moderately severe Alzheimer's disease, those treated with rivastigmine tartrate showed significantly better cognitive function compared to those who received a placebo.

The study included an initial 26-week double-blind phase followed by a 26-week open-label extension, demonstrating the sustained efficacy of rivastigmine over a full year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer's disease. Farlow, M., Anand, R., Messina, J., et al.[2022]

A study involving 40 healthy men demonstrated that the generic formulation of rivastigmine is bioequivalent to the brand Exelon, with similar pharmacokinetic profiles as shown by comparable AUC and Cmax values.

Both the generic and reference formulations were well tolerated by participants, indicating that the generic version is a safe alternative to the brand-name drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers. Abhyankar, D., Shedage, A., Gole, M., et al.[2018]

Rivastigmine tartrate is effective in improving or maintaining cognitive function, daily living activities, and behavior in patients with mild to moderate Alzheimer's disease, based on clinical trials lasting up to 52 weeks.

The most common side effects are mild to moderate gastrointestinal issues, and treatment may lead to cost savings in care, particularly by delaying the need for institutionalization, especially in patients with moderate Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of rivastigmine: a reversible cholinesterase inhibitor. Williams, BR., Nazarians, A., Gill, MA.[2022]

In a study of 892 patients with probable Alzheimer's disease, both rivastigmine patches and capsules significantly improved activities of daily living (ADLs) compared to placebo after 24 weeks, indicating their efficacy in managing symptoms.

Rivastigmine patches showed a lower incidence of gastrointestinal side effects compared to capsules, making them a safer alternative for patients who may be sensitive to such side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of rivastigmine patch and capsules on activities of daily living in Alzheimer's disease. Grossberg, G., Meng, X., Olin, JT.[2015]

Rivastigmine, whether administered as a patch or capsule, significantly improves cognitive function in patients with mild to severe Alzheimer's disease compared to placebo, as shown in a meta-analysis of 17 studies.

The rivastigmine patch is more effective than the capsule in reducing cognitive decline, as indicated by a greater improvement in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe Alzheimer's disease: a meta-analysis. Su, J., Liu, Y., Liu, Y., et al.[2018]

An 87-year-old male with dementia experienced severe adverse effects, including nausea, vomiting, and renal failure, after mistakenly applying six rivastigmine patches simultaneously, leading to his death from uremia due to dehydration.

This case highlights the critical need for clear labeling and instructions for rivastigmine patches to prevent medication errors, emphasizing that only one patch should be applied at a time to avoid overdose and serious health consequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fatal outcome after unintentional overdosing of rivastigmine patches. Lövborg, H., Jönsson, AK., Hägg, S.[2019]

In the phase III OPTIMA trial, patients with mild to moderate Alzheimer's disease showed significant benefits in functional and cognitive decline when their rivastigmine dose was increased from a 10 cm² patch to a 15 cm² patch after 24 weeks.

The 15 cm² patch was generally well tolerated, with fewer patients discontinuing treatment due to adverse events compared to the 10 cm² patch, indicating a favorable benefit-risk profile for increasing the dose in patients who had previously experienced decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivastigmine transdermal patch 13.3 mg/24 h: a review of its use in the management of mild to moderate Alzheimer's dementia. Frampton, JE.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC1974793/

EXACT: rivastigmine improves the high prevalence of ...

A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to ...

2.

withpower.com

withpower.com/trial/phase-2-anticholinergics-toxicity-5-2024-a0b93

Rivastigmine for Delirium · Info for Participants

Rivastigmine tartrate is effective in improving or maintaining cognitive function, daily living activities, and behavior in patients with mild to moderate ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/27111084/

Effects on agitation with rivastigmine patch monotherapy ...

In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors.

4.

synapse.patsnap.com

synapse.patsnap.com/drug/82ea43f4acf8466e97fd857d201c4f61

Rivastigmine Tartrate - Drug Targets, Indications, Patents

Clinical Results associated with Rivastigmine Tartrate. Login to view more data. 100 Translational Medicine associated with Rivastigmine Tartrate. Login to ...

5.

go.gale.com

go.gale.com/ps/i.do?id=GALE%7CA260582468&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=00126667&p=HRCA&sw=w

Rivastigmine transdermal patch: a review of its use in the ...

Rivastigmine, a cholinesterase inhibitor, is available as a transdermal patch (Exelon[R] patch, Rivastach[R] patch, Prometax[R] patch) for the treatment of ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10293131/

Rivastigmine Use in the Treatment of Antimuscarinic Delirium

Rivastigmine appears to be safe in this population. Larger studies are warranted to determine the optimal dosing, including route(s) of administration, and to ...

7.

knighttx.com

knighttx.com/CA/products_info/PATCH-PM_Approved15Aug2023-ENG.pdf

EXELON® PATCH (Rivastigmine Hydrogen Tartrate)

Symptoms: Manifestations include nausea, vomiting, diarrhea, abdominal pain, dizziness,. Page 8. EXELON® PATCH (Rivastigmine Hydrogen Tartrate).

8.

scholarworks.indianapolis.iu.edu

scholarworks.indianapolis.iu.edu/bitstreams/34bb2b63-ba9b-4935-b09e-b02950f1640c/download

A 24-Week, Open-Label Extension Study to Investigate the ...

the long-term safety of rivastigmine 13.3 mg/24 h patch in patients with severe AD. ... (rivastigmine tartrate) prescribing Information. 2013. Available at: http ...

9.

assets.ctfassets.net

assets.ctfassets.net/plyq12u1bv8a/1FBX8AcsmZWE2fi3sQfOQm/6d66faadfc19ecdd339ed0ac9333e152/PG212_Rivastigmine__Exelon__v2.pdf

Oscar Clinical Guideline: Rivastigmine (Exelon) (PG212, Ver. 2)

○ Rivastigmine Tartrate Oral capsule. ○ Rivastigmine Transdermal Patch - 24 ... There are no high quality large clinical trials to support the safety and efficacy ...