Midodrine for Low Blood Pressure

(SCI Trial)

Recruiting at 2 trial locations

Overseen By Matt G. Maher, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: James J. Peters Veterans Affairs Medical Center

Disqualifiers: Psychiatric disorder, Stroke, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 visits

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of Midodrine Hydrochloride and other treatments for individuals with low blood pressure due to spinal cord injuries (SCI). The study examines how these treatments impact symptoms such as dizziness when standing and overall comfort. Participants will test various treatments, including medication and compression garments, to determine the most beneficial options. This trial targets individuals who have had a spinal cord injury for over a year, with injuries from the neck to the upper back, and who are unable to walk or require a ventilator. As a Phase 4 trial, the treatment has already received FDA approval and demonstrated effectiveness, allowing researchers to understand its benefits for a broader patient population.

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.

What is the safety track record for these treatments?

Research has shown that midodrine often treats low blood pressure, particularly when it drops suddenly upon standing, a condition known as orthostatic hypotension. The FDA has approved it for this use, and it has been available for some time.

A study with 171 patients found that midodrine is generally safe, though it can sometimes raise blood pressure even at rest. Common side effects include tingling or itching of the skin, chills, and increased urination frequency. Most people tolerate it well, but monitoring blood pressure is crucial to prevent excessive increases.

For those considering a trial involving midodrine, this information may clarify its safety profile. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for low blood pressure, like fludrocortisone and droxidopa, work by increasing blood volume or directly raising blood pressure through different pathways. However, midodrine is unique because it directly acts on the blood vessels to tighten them, leading to an increase in blood pressure. This mechanism provides a more targeted approach, potentially offering rapid relief from symptoms like dizziness and lightheadedness. Researchers are excited about midodrine because it offers a promising alternative for patients who don't respond well to existing treatments, potentially improving their quality of life by managing symptoms more effectively.

What evidence suggests that this trial's treatments could be effective for low blood pressure?

Research has shown that midodrine effectively treats orthostatic hypotension, a condition where blood pressure drops upon standing. One study found that midodrine improved blood pressure and was well-tolerated by patients. It raises blood pressure by narrowing blood vessels. Although some debate exists about its overall effectiveness, midodrine is approved for treating low blood pressure in certain conditions. This trial will evaluate midodrine alongside other treatments, such as droxidopa and compression garments, to determine their effects on orthostatic hemodynamics and related symptoms. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with a spinal cord injury (SCI) that happened at least a year ago, affecting the C1-T6 regions of the spine. Participants must be non-ambulatory and have an AIS grade A, B, or C, indicating varying levels of impairment.

Inclusion Criteria

I have had a spinal cord injury due to trauma.

My spinal cord injury is classified as AIS A, B, or C.

It has been over a year since my injury.

Exclusion Criteria

I am currently experiencing a psychiatric disorder.

I have or might have cancer.

I have been diagnosed with Alzheimer's Disease or dementia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive non-pharmacological and pharmacological anti-hypotensive treatment interventions, including midodrine, droxidopa, and compression garments, over 6 laboratory visits

6 visits

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on orthostatic hemodynamics and symptoms

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Midodrine Hydrochloride

Trial Overview The study is testing Midodrine Hydrochloride to see how it affects blood pressure regulation in people with SCI who experience low blood pressure when they stand up (orthostatic hypotension).

How Is the Trial Designed?

Group I: Study 2 Experimental Treatment 1 Intervention

Determine the effects of compression garments, midodrine, and droxidopa, compared to placebo, on orthostatic hemodynamics, symptoms of AD and OH and reporting of fatigue and thermal comfort.

Group II: Study 1 Experimental Treatment 1 Intervention

Twenty-five participants will be asked to visit the laboratory on 6 occasions, for an open-label, dose escalation trial to determine the effect of midodrine and droxidopa on supine and seated blood pressure and on symptoms of autonomic dysreflexia and orthostatic hypotension.

Midodrine Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as ProAmatine for:

• Orthostatic hypotension

Approved in European Union as Orvaten for:

• Orthostatic hypotension

Approved in Canada as Midodrine Hydrochloride for:

• Orthostatic hypotension

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Kessler Foundation

Collaborator

Trials

190

Recruited

11,300+

Published Research Related to This Trial

Oral midodrine effectively increases standing systolic blood pressure and improves symptoms of orthostatic hypotension, such as dizziness and light-headedness, making it a valuable treatment option for this condition.

Midodrine is well tolerated with common side effects including piloerection and urinary retention, and the risk of supine hypertension can be managed by timing the last dose appropriately, enhancing its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. McClellan, KJ., Wiseman, LR., Wilde, MI.[2018]

In a study involving 171 patients, midodrine significantly improved standing systolic blood pressure and reduced symptoms of lightheadedness in individuals with neurogenic orthostatic hypotension over a 6-week period.

Midodrine was found to be safe, with common side effects including pilomotor reactions, urinary retention, and supine hypertension, but overall it effectively alleviated symptoms and improved patient-reported outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. Low, PA., Gilden, JL., Freeman, R., et al.[2016]

Midodrine effectively increases standing blood pressure and alleviates symptoms of orthostatic hypotension, such as weakness and fatigue, without causing cardiac stimulation, making it a safe option for patients.

In comparative studies, midodrine demonstrated at least equal efficacy to other sympathomimetic agents while causing fewer severe side effects, suggesting it is a preferable choice for managing hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders. McTavish, D., Goa, KL.[2018]

Midodrine, used for treating orthostatic hypotension, can lead to severe hypertension when the patient is lying down, particularly during general anesthesia.

A specific case is presented where a patient experienced significant hypertension while under anesthesia, highlighting the need for careful monitoring and preventive measures when using midodrine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supine hypertension during general anesthesia in a patient taking midodrine. Chaimberg, KH., Travis, KW.[2022]

Pyridostigmine bromide significantly improves standing blood pressure in patients with orthostatic hypotension (OH) without causing worsening of supine hypertension, based on a study involving 58 patients.

The treatment notably reduced the fall in standing diastolic blood pressure, indicating that it may enhance total peripheral resistance, which helps alleviate symptoms of OH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Singer, W., Sandroni, P., Opfer-Gehrking, TL., et al.[2018]

Midodrine hydrochloride effectively stopped syncope attacks in a 10-year-old boy with severe orthostatic hypotension, demonstrating its efficacy as a treatment for this condition.

Despite its benefits, midodrine caused significant side effects, including supine hypertension, which persisted for 19 days after stopping the medication, highlighting the need for careful monitoring of patients after treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child. Olgar, S., Omeroglu, RE.[2018]

In a double-blind, placebo-controlled study involving 19 patients with severe symptomatic orthostatic hypotension, midodrine significantly delayed the onset of syncopal symptoms compared to placebo, with an average difference of 521 seconds.

Midodrine was found to be well-tolerated, with only mild to moderate adverse events reported, none of which were deemed related to the medication, indicating its safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study. Smith, W., Wan, H., Much, D., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7900270/

Midodrine for orthostatic hypotension - PMC The reviewers concluded that there was insufficient evidence to recommend midodrine for orthostatic hypotension.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6952305/

Efficacy of atomoxetine versus midodrine for neurogenic ... The primary outcome was an improvement in orthostatic blood pressure (BP) drop (maximum BP change from supine to 3 min after standing) at 1 month.

3. sciencedirect.com sciencedirect.com/science/article/pii/000293439390230M

A double-blind, placebo-controlled study with midodrine We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

4. ahajournals.org ahajournals.org/doi/10.1161/hypertensionaha.114.04225

Efficacy of Atomoxetine Versus Midodrine for the Treatment ... The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in ...

5. mayoclinic.org mayoclinic.org/drugs-supplements/midodrine-oral-route/description/drg-20064821

Midodrine (oral route) - Side effects & dosage Midodrine is used to treat low blood pressure (hypotension). It works by stimulating nerve endings in blood vessels, causing the blood vessels to tighten.

6. webmd.com webmd.com/drugs/2/drug-14042/midodrine-oral/details

Midodrine (Orvaten, ProAmatine): Uses, Side Effects, ... Midodrine is commonly used to treat low blood pressure that causes symptoms, particularly low blood pressure upon standing (orthostatic hypotension).

7. tga.gov.au tga.gov.au/sites/default/files/auspar-midodrine-hydrochloride-210716-pi-03.pdf

Attachment: Product Information: Midodrine Hydrochloride The safety and efficacy of midodrine was evaluated in a published randomised, double-blind, parallel group Phase III study (Low 1997, n=171) in ...

8. drugs.com drugs.com/mtm/midodrine.html

Midodrine Uses, Side Effects & Warnings Midodrine can increase blood pressure even when you are at rest. midodrine should be used only if you have severely low blood pressure that ...