Blood Pressure Medications for Stroke

(PRESS Trial)

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: MAO-I

Disqualifiers: ICH, Heart failure, Myocardial infarction, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how boosting blood pressure might aid individuals who recently experienced a major stroke called an LVO (large vessel occlusion) and are undergoing a procedure to remove the blockage. Researchers aim to determine if raising blood pressure with medications like norepinephrine and phenylephrine can prevent further brain damage during treatment. This trial specifically targets those who had a stroke affecting the brain's front circulation and are treated within 24 hours of the stroke. The trial seeks to establish the safety and feasibility of this approach. Individuals who recently experienced an ischemic stroke and are undergoing endovascular therapy might qualify for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken Monoamine oxidase inhibitors (MAO-I) in the last 7 days.

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

In a previous study, phenylephrine improved short-term brain function and reduced areas with low blood flow in the brain. While promising, phenylephrine can also raise blood pressure, potentially affecting heart function, especially in individuals with heart problems.

Less direct research exists on using norepinephrine for stroke, but it is generally used to raise blood pressure in other medical situations. This provides some insight into its safety, though not specifically for stroke patients.

As this is an early phase trial, the main goal is to determine the safety of these treatments for stroke patients. Limited safety information may be available for this specific use. Prospective participants should be aware that researchers will closely monitor responses to these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using norepinephrine and phenylephrine for stroke treatment because these medications work by increasing blood pressure to improve blood flow in the brain, which is quite different from the standard treatments like clot-busting drugs. Most current therapies aim to dissolve clots or prevent new ones, but phenylephrine, for example, is used to induce hypertension, which could help open blocked blood vessels more quickly. This approach might offer a faster way to restore blood circulation during a stroke, potentially leading to better outcomes and quicker recoveries for patients.

What evidence suggests that these blood pressure medications could be effective for stroke patients?

Research has shown that phenylephrine, which participants in this trial may receive, can help with certain stroke conditions by raising blood pressure. One study showed that using phenylephrine to increase blood pressure temporarily improved stroke symptoms, enhanced brain function, and reduced brain damage. Another study found that phenylephrine effectively raised blood pressure and improved blood flow to the brain. These findings suggest that phenylephrine might help manage stroke by increasing blood flow during treatment. ^{1 3 6 7 8}

Who Is on the Research Team?

Nils H Petersen, MD, MSc

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific type of stroke (anterior circulation acute ischemic stroke) who can start treatment within 24 hours. They must be undergoing endovascular thrombectomy and have certain imaging findings that show a mismatch in blood flow to the brain. People with very high blood pressure, recent heart issues, or those on certain medications like MAO inhibitors cannot participate.

Inclusion Criteria

I have undergone a procedure to remove a blood clot from my artery.

Your genetic test shows a mismatch ratio higher than 1.8.

The size of the damaged area in the brain is less than 70 milliliters.

Exclusion Criteria

I have severe heart issues, including heart failure or angina that affects my daily activities.

I have had a heart attack in the last 6 months.

I was suspected to have aortic dissection when I was admitted.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Standard of Care Monitoring

Monitoring beat-to-beat blood pressure and other hemodynamic parameters in 20 patients receiving standard of care therapy

2.5 hours

Stage 2: Blood Pressure Augmentation

Blood pressure augmentation therapy using intravenous fluids and phenylephrine or norepinephrine infusion to increase baseline systolic blood pressure by 20% to at least 160 mmHg until blood vessel recanalization is achieved or the thrombectomy procedure is completed

2.5 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of symptomatic intracranial hemorrhage and serious adverse events

72 hours

What Are the Treatments Tested in This Trial?

Interventions

• Norepinephrine
• Phenylephrine

Trial Overview The study is testing whether increasing blood pressure using drugs Phenylephrine or Norepinephrine can limit damage from strokes caused by large vessel blockage. It's an early-stage trial to see if this approach is practical and tolerable for patients when given alongside mechanical clot removal.

How Is the Trial Designed?

Group I: Induced hypertension Experimental Treatment 2 Interventions

The scientists will investigate the potential consequences of increasing baseline systolic blood pressure with intravenous fluids and phenylephrine by 20% to at least 160 mmHg until blood vessel recanalization is achieved or the thrombectomy procedure is completed. The maximum allowed SBP is 220 mmHg or 180 mmHg, if intravenous TPA was administered.

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

Approved in United States as Levophed for:

• Severe, acute hypotension
• Cardiac arrest

Approved in Canada as Norepinephrine Bitartrate for:

• Severe, acute hypotension
• Cardiac arrest

Approved in European Union as Noradrenaline for:

• Severe, acute hypotension
• Cardiac arrest

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

Topical phenylephrine can cause severe hypertension due to its action on alpha-adrenergic receptors, which is a significant safety concern, especially in pediatric patients.

In this case, a pediatric patient experienced acute pulmonary edema after receiving a large dose of phenylephrine followed by beta-blockers, highlighting the potential risks of combining these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary edema following phenylephrine intranasal spray administration during the induction of general anesthesia in a child. Son, JS., Lee, SK.[2022]

Hypertensive patients should avoid using adrenergic agents for blood pressure control, with nasal phenylephrine hydrochloride being the safest option among them, while pseudoephedrine may also be safe.

Ibuprofen can raise blood pressure if taken at maximum over-the-counter doses for extended periods, highlighting the need for caution with nonprescription medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonprescription drugs and hypertension. Which ones affect blood pressure? Bradley, JG.[2019]

A review of 12 clinical studies found that intranasal phenylephrine appears to be safe for patients with controlled hypertension, based on one double-blind randomized trial.

The evidence regarding the safety of other sympathomimetic decongestants like phenylpropanolamine and pseudoephedrine in hypertensive patients is limited and unclear, suggesting that the belief they are unsafe is not strongly supported by research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are oral decongestants safe in hypertension? An evaluation of the evidence and a framework for assessing clinical trials. Radack, K., Deck, CC.[2013]

In a study of 86 pre-eclamptic women undergoing cesarean sections, both phenylephrine and norepinephrine were found to be equally effective in treating postspinal hypotension, with no significant differences in neonatal outcomes as measured by umbilical artery pH.

However, the phenylephrine group experienced fewer hypotensive episodes and lower heart rates compared to the norepinephrine group, suggesting it may be a safer option in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised double-blind comparison of phenylephrine and norepinephrine for the management of postspinal hypotension in pre-eclamptic patients undergoing caesarean section. Mohta, M., R, L., Chilkoti, GT., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8240891/

Cerebrovascular Response to Phenylephrine in Traumatic ... Primary: Examine PE-induced hypertension ... Phenylephrine-induced hypertension does not improve outcome after closed head trauma in rats.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6885575/

Therapeutic-induced hypertension in patients with ... In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint ...

3. journal.chestnet.org journal.chestnet.org/article/S0012-3692(20)33095-6/fulltext

THE EFFICACY AND SAFETY OF USING PHENYLEPHRINE ... A randomized trial (RT) utilizing PE to target an elevated SBP showed a short-term improvement in the NIHSS, cognitive score, and volume of hypoperfused tissue.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0007091217324480

Effect of phenylephrine on the haemodynamic state and ... Phenylephrine prevented hypotension in the upright position primarily by maintaining preload and increasing systemic vascular resistance (P=0.01), and was ...

5. ahajournals.org ahajournals.org/doi/10.1161/hypertensionaha.109.146290

Influence of Changes in Blood Pressure on Cerebral ... These findings indicate that cerebral blood flow closely follows pharmacological-induced changes in blood pressure in otherwise healthy humans.

6. rjid.com.ro rjid.com.ro/articles/2023.4/RJID_2023_4_Art-01.pdf

Update on the efficiency and safety of orally administered ... Both in vitro and in vivo clinical pharmacology data indicate that neither the recommended doses nor higher doses of oral PHE demonstrate ...

7. ahajournals.org ahajournals.org/doi/10.1161/01.str.0000075293.45936.fa

Stroke Associated With Sympathomimetics Contained in ... Stroke occurred after recommended doses of PPA (50 to 75 mg) in 32% and pseudoephedrine (60 mg) in 50% of patients. Eight patients had acute hypertension at ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4500855/

simulation and narrative review An increase in blood pressure with associated impairment in myocardial perfusion was seen when phenylephrine was administered to patients with underlying ...