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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

An open label, prospective, single center, pilot trial to assess feasibility and tolerability of short term blood pressure augmentation to minimize infarct progression in acute LVO stroke patients undergoing endovascular therapy.

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.

What data supports the effectiveness of the drug Norepinephrine and Phenylephrine for stroke?

A pilot study found that using phenylephrine to raise blood pressure in acute stroke patients was feasible and safe, with some patients showing neurological improvement. However, there are concerns that norepinephrine might worsen certain conditions like cerebral vasospasm after a specific type of brain hemorrhage. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Phenylephrine, one of the medications mentioned, is generally considered safe for people with controlled high blood pressure when used as a nasal spray, but it can cause severe high blood pressure and other issues if used inappropriately or in large doses. It's important to use these medications carefully and under medical supervision, especially if you have high blood pressure. ^{6 7 8 9 10}

How does the drug Norepinephrine, Phenylephrine differ from other treatments for stroke prevention?

Norepinephrine and Phenylephrine are primarily used to increase blood pressure in acute settings, which is different from most stroke prevention drugs that focus on lowering blood pressure. This makes them unique as they are not typically used for long-term stroke prevention but rather for managing acute blood pressure changes. ^{5 11 12 13 14}

Research Team

Nils H Petersen, MD, MSc

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Labetalol Use Is Associated With Increased In-Hospital Infection Compared With Nicardipine Use in Intracerebral Hemorrhage. [2018]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A pilot study of drug-induced hypertension for treatment of acute stroke. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Norepinephrine as a potential aggravator of symptomatic cerebral vasospasm: two cases and argument for milrinone therapy. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

β-Blockers associated with no class-specific survival benefit in acute intracerebral hemorrhage. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Hypertensive Urgency Associated With Xenadrine EFX Use. [2019]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Treatment of hypertension in mild asthmatic patients with atenolol. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

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

11. United States pubmed.ncbi.nlm.nih.gov

Antihypertensive treatment and stroke prevention: from recent meta-analyses to the PRoFESS trial. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Blood pressure lowering in patients with cerebrovascular disease: results of the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) pilot phase. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Arterial hypertension and stroke prevention: an update. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. [2022]