Rivastigmine for Delirium

(RIVA-AP Trial)

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 be taking: Physostigmine

Must not be taking: Sodium bicarbonate, Vasopressors

Disqualifiers: Pregnancy, Seizure disorder, Asthma, 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: Unknown

Duration: 8-36 hours

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for antimuscarinic delirium (AMD), a type of confusion and agitation caused by certain poisons. The study explores whether rivastigmine, a medication with longer-lasting effects, can prevent AMD from recurring after initial treatment with physostigmine. Participants will be divided into two groups: one will receive rivastigmine, and the other will receive a placebo (a pill with no active medication). This trial may suit individuals who have experienced AMD, achieved initial control with physostigmine, and can take oral medication. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rivastigmine is generally safe for people. A small initial study found that stroke patients with delirium tolerated the drug well, even with rapid dose increases. Most of these patients improved in their delirium after treatment. Another study involving individuals with Alzheimer's disease found significant benefits for those taking rivastigmine, suggesting its safety. Although larger studies are needed to determine the optimal dose and administration method, these findings indicate that rivastigmine holds promise for treating conditions like antimuscarinic delirium. ^{1 2 3 4 5}

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

Unlike the standard treatments for delirium, which often rely on antipsychotics like haloperidol, rivastigmine offers a different approach by enhancing cholinergic activity in the brain. This unique mechanism targets the neurotransmitter acetylcholine, potentially improving cognitive function and reducing symptoms of delirium more effectively. Researchers are excited about rivastigmine because it may provide a faster and more targeted response, offering relief in just hours rather than days.

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

This trial will compare rivastigmine with a placebo for treating delirium. Studies have shown that rivastigmine can help treat delirium. In stroke patients with delirium, most improved after taking rivastigmine. Another study found that the drug helped people with mild to moderate memory and thinking problems perform better in daily activities. However, some research showed that rivastigmine did not affect the frequency or duration of delirium in older adults without memory issues. Overall, these findings suggest rivastigmine might be helpful, especially when delirium is already present. ^{2 4 6 7 8}

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 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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Rivastigmine

Trial Overview

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.

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

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]

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]

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]

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]

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]

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]

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]

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In patients without delirium in the acute phase of stroke, the results of neuropsychological study were better (p<0,001) than in patients with delirium.

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pmc.ncbi.nlm.nih.gov/articles/PMC2556687/

A pilot study of rivastigmine in the treatment of delirium after ...

Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment.

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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 ...

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Rivastigmine patch (Exelon patch) compared to melatonin ...

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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 ...

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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 ...