Vasopressor Titration for Low Blood Pressure

(OVATION-65 Trial)

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Université de Sherbrooke

Disqualifiers: Spinal cord injury, Brain injury, Organ transplant, others

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

Compensation: Varies

Number of Visits: 6

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how maintaining slightly lower blood pressure affects organ health and survival in older patients. It compares usual care to a method called "Permissive Low Blood Pressure," where medication called vasopressors keeps blood pressure in a specific, slightly lower range. Participants must be 65 or older and have been on vasopressors for 12 hours or less due to low blood pressure not caused by bleeding or specific heart issues. The trial aims to determine if a lower blood pressure target can safely benefit patients without causing harm. As an unphased trial, this study offers participants a unique opportunity to contribute to pioneering research that could redefine blood pressure management in older adults.

Do I have to stop taking my current medications for 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 coordinators or your doctor.

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

Research has shown that maintaining a slightly lower blood pressure, with a mean arterial pressure (MAP) between 60-65 mmHg, can be safe for some patients. A review of 11 clinical trials found that targeting a lower MAP, such as 50-70 mmHg, might reduce the risk of death compared to higher blood pressure targets. This suggests that slightly lower blood pressure could be a safe option.

In another study, patients in the low blood pressure group maintained the target MAP of 60-65 mmHg about half the time. This indicates that achieving and sustaining this target is possible and safe in practice.

These studies suggest that maintaining lower blood pressure can be well-tolerated. However, individual experiences can vary, so discussing participation in a trial with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the permissive low blood pressure technique because it could change how we manage low blood pressure during critical care. Unlike traditional treatments that often aim to maintain a higher mean arterial pressure (MAP) using vasopressors, this approach targets a MAP of 60-65 mmHg. By avoiding excessive use of vasopressors, the method might reduce potential side effects and complications associated with high doses of these medications. This strategy could offer a safer and more tailored way to support patients with low blood pressure, potentially improving outcomes without the risks linked to aggressive blood pressure management.

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

In this trial, participants will be assigned to different treatment arms to evaluate blood pressure management strategies. One arm will follow the "Usual Care" approach, where patients receive standard care according to local practices. Another arm will target a mean arterial pressure (MAP) of 60-65 mmHg, adjusting vasopressors to maintain this range. Research has shown that allowing slightly lower blood pressure might benefit older patients. In the 65 trial, patients maintained a blood pressure target of 60-65 mmHg, and the results were promising. This approach used fewer vasopressors, which are drugs that raise blood pressure. The trial suggested that maintaining slightly lower blood pressure could save money and reduce the risks associated with excessive vasopressor use. These findings support the idea that this method might help manage organ damage and improve survival in very sick patients. ^{1 3 5 6 7}

Who Is on the Research Team?

François Lamontagne, MD FRCPC MSc

Principal Investigator

University of Sherbrooke and CIUSSS de l'Estrie-CHUS

Neill Adhikari, MDCM MSc

Principal Investigator

Sunnybrook Health Sciences Centre, University of Toronto

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older who have low blood pressure due to vasodilation. They must have started on vasopressors within the last 12 hours and are expected to need them for at least another 6 hours, as determined by their medical team.

Inclusion Criteria

I started vasopressors within 12 hours of ICU admission after getting enough fluids.

My doctors plan to continue my blood pressure medication for at least 6 more hours.

I am 65 years old or older.

Exclusion Criteria

The treating physician(s) lacks equipoise regarding the overall effects of permissive hypotension versus usual care on patient important outcomes.

I have had an organ transplant in the past year.

Death perceived as imminent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to target MAP 60-65 mmHg vs. usual care and receive vasopressor therapy accordingly

28 days

Daily monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including organ function and cognitive assessments

6 months

Regular follow-up assessments, including phone call at 6 months

Long-term follow-up

Assessment of mortality and cognitive impairment at 6 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Permissive Low Blood Pressure
• Usual care

Trial Overview OVATION-65 aims to compare two blood pressure management strategies in older patients: a lower target mean arterial pressure (MAP) of 60-65 mmHg versus usual care practices. The study will assess organ injury markers and survival rates.

How Is the Trial Designed?

Group I: MAP target 60-65 mmHg Experimental Treatment 1 Intervention

Treating teams will adjust vasopressors to a target MAP range of 60 to 65 mmHg, avoiding vasopressor-induced MAP above this range.

Group II: Usual Care Active Control 1 Intervention

Patients in the control arm will receive usual care (as per local practices).

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568056/

Methods - Reduced exposure to vasopressors through ... - NCBI The 65 trial was a pragmatic, multicentre, parallel-group, open-label RCT of reduced exposure to vasopressors through permissive hypotension.

2. account.icnarc.org account.icnarc.org/Our-Research/Studies/Sixty-Five/About

65 Trial The 65 trial evaluated, in a pragmatic, randomised clinical trial, the clinical and cost-effectiveness of using a strategy of permissive hypotension (MAP target ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1441277225000079

Mean arterial pressure in critically ill adults receiving ... This dissociation between target and actual MAP was also demonstrated in the 65 trial, where the 60–65 mmHg MAP group had a median MAP of 66.7 mmHg.

4. journals.sagepub.com journals.sagepub.com/doi/full/10.1177/1751143719870088

Protocol for the 65 randomised clinical trial The primary aim of the 65 trial is to evaluate the clinical and cost-effectiveness of permissive hypotension (MAP target range 60–65 mmHg during ...

5. isrctn.com isrctn.com/pdf/10580502

The 65 trial The aim of this study is to evaluate the clinical and cost-effectiveness of permissive hypotension (MAP target of 60 - 65 mmHg during.

6. emcrit.org emcrit.org/pulmcrit/65trial/

PulmCrit - The 65 trial: Is 60 the new 65? On average, patients in the permissive hypotension group achieved the target MAP of 60-65 mm about half the time: The MAP was on average 6 mm ...

7. pulmccm.org pulmccm.org/p/are-usual-vasopressor-doses-causing

Are usual vasopressor doses causing unrecognized harm? Maintaining a mean arterial pressure (MAP) of 65 mm Hg has been advised for patients with sepsis and other forms of vasodilatory shock.