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Acute Respiratory Distress SyndromePhase 3NCT06013319

Effect of Esmolol on Oxygenation Index in Patients With Acute Respiratory Distress Syndrome

A Phase 3 study testing Esmolol in people with Acute Respiratory Distress Syndrome, run by Zhiming Jiang at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary and/or extrapulmonary causes, characterized by intractable hypoxemia. Studies have shown that the sympathetic nervous system is over-activated in patients with acute respiratory distress syndrome. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Respiratory Distress Syndrome
What is being tested?
Esmolol
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
178 participants
Where
1 siteChina
Study dates
20 Feb 2023to 30 Oct 2026
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Meeting the 2012 Berlin diagnostic criteria for acute respiratory distress syndrome;
  • Aged between 18-65 years (inclusive);
  • 95 times/min ≤ heart rate ≤120 times/min;
  • The patient needs to undergo endotracheal intubation mechanical ventilation after condition assessment;
  • Obtain the informed consent of the patient or his legal representative.

Who cannot join

  • Bradycardia and second degree or more atrioventricular block;
  • Long-term use of beta-blockers;
  • Combined with emphysema, asthma and other β-blocker contraindicated diseases;
  • Cardiac insufficiency (NYHA grade Ⅲ or Ⅳ);
  • Pregnancy

Trial locations and contacts

1 site in 1 country.

Quanzhen Wang, doctor contact

15562570205

wangquanzhen1986@163.com

China1 site, 1 recruiting
  • Department of Intensive Care Medicine

    Jinan, Shandong, 250014

    Quanzhen Wang, doctor

    Recruiting

Other trials in China

About this study

Official title: Effects of Esmolol on Oxygenation Index by Controlling Heart Rate in Patients With Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary and/or extrapulmonary causes, characterized by intractable hypoxemia. Studies have shown that the sympathetic nervous system is over-activated in patients with acute respiratory distress syndrome. A large retrospective study showed a reduction in mortality in ARDS patients treated with oral β1 blockers before admission, and this beneficial effect of β1 blockers applies to ARDS patients with or without cardiac disease. Esmolol is an ultra-short-acting selective β1 receptor blocker. Previous studies have shown that esmolol can improve oxygenation and reduce the levels of inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thereby alleviating pulmonary injury. According to the literature and our previous clinical observations, we made the following hypothesis: When Estolol is applied to various ARDS patients undergoing mechanical ventilation in ICU, it can control the heart rate by inhibiting β-adrenergic receptor, which can ultimately improve the oxygenation index of patients and shorten the mechanical ventilation time. This project intends to include ARDS patients with optimal hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after conventional treatment, but ≤120 beats/min. They are randomly divided into control group and Esmolol treatment group to study the effects of esmolol on patients' oxygenation index, mechanical ventilation time, hemodynamics, function of various organs and inflammation level. The aim of this study is to optimize the treatment of ARDS patients.

Read the detailed description

At present, there are few studies on Esmolol in acute respiratory distress syndrome. However, previous studies have shown that Esmolol can improve oxygenation and reduce the levels of inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thus alleviating pulmonary injury. Considering that a considerable number of ARDS patients in the intensive care unit suffer from sepsis, we conducted this study to explore the application timing of esmolol therapy and whether esmolol can improve the symptoms and prognosis of ARDS patients. Based on the literature and our previous clinical observations, we make the following assumptions: Esmolol is applied to various ARDS patients receiving mechanical ventilation in ICU. By inhibiting the β-adrenergic receptor to control the heart rate, it can ultimately improve the oxygenation index of patients, shorten the mechanical ventilation time, achieve tracheal intubation extraction as soon as possible, and reduce the 28-day mortality. At the same time, esmolol can also improve the function of various organs of patients and reduce the level of inflammatory factors. This project intends to include ARDS patients with optimal hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after conventional treatment, but ≤120 beats/min. They are randomly divided into control group and Esmolol treatment group to study the effects of esmolol on patients' oxygenation index, mechanical ventilation time, hemodynamics, function of various organs and inflammation level. To optimize the treatment of ARDS patients.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary and/or extrapulmonary causes, characterized by intractable hypoxemia. ARDS is the most common cause of respiratory failure in severe patients, and also the main factor leading to poor prognosis in severe patients. In recent years, although the research on ARDS has continued to go deeper, clinical treatment still remains in the stage of lung protective ventilation and restricted fluid management, and there is still a lack of specific drug therapy, and the fatality rate is still as high as 40%.

Studies have shown that the sympathetic nervous system is over-activated in patients with acute respiratory distress syndrome. Because 75 to 80 percent of myocardial adrenergic receptors are β1 type, and adrenergic stress is primarily mediated by beta receptors, the heart is a prime target for sympathetic overstimulation. Elevated heart rate is associated with adverse outcomes in patients with severe infection and represents the severity of the disease.Another large retrospective study showed a reduction in mortality in ARDS patients treated with oral β1 blockers before admission, and this beneficial effect of β1 blockers applies to ARDS patients with or without cardiac disease.

Esmolol is an ultra-short-acting selective β1 receptor blocker, which mainly inhibits β1 receptor by competing for catecholamine binding sites in myocaroma, and has the effect of slowing resting and exercise heart rate, lowering blood pressure, and reducing myocardial oxygen consumption. Esmolol is a metabolite coupled with enzyme, so its distribution half-life is very short, intravenous injection begins to take effect 1-2 min, elimination half-life is only 9min, easy to control, high safety, and remarkable effect. There have been numerous studies on esmolol in sepsis. For patients with septic shock, the use of esmolol can reduce heart rate to the target level, but does not increase the incidence of adverse events, and does not reduce microcirculation perfusion, and can improve the hemodynamics and 28-day mortality of patients. In addition, both animal and human experiments have proved that Esmolol can reduce the release of inflammatory factors in sepsis, improve inflammatory response, and protect cardiac and renal function.

At present, there are few studies on Esmolol in acute respiratory distress syndrome. However, previous studies have shown that Esmolol can improve oxygenation and reduce the levels of inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thus alleviating pulmonary injury. Considering that a considerable number of ARDS patients in the intensive care unit suffer from sepsis, we conducted this study to explore the application timing of esmolol therapy and whether esmolol can improve the symptoms and prognosis of ARDS patients. Based on the literature and our previous clinical observations, we make the following assumptions: Esmolol is applied to various ARDS patients receiving mechanical ventilation in ICU. By inhibiting the β-adrenergic receptor to control the heart rate, it can ultimately improve the oxygenation index of patients, shorten the mechanical ventilation time, achieve tracheal intubation extraction as soon as possible, and reduce the 28-day mortality. At the same time, esmolol can also improve the function of various organs of patients and reduce the level of inflammatory factors. This project intends to include ARDS patients with optimal hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after conventional treatment, but ≤120 beats/min. They are randomly divided into control group and Esmolol treatment group to study the effects of esmolol on patients' oxygenation index, mechanical ventilation time, hemodynamics, function of various organs and inflammation level. To optimize the treatment of ARDS patients.

To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index. A total of 187 patients aged 18-65 years who met the 2012 Berlin diagnostic criteria for acute respiratory distress syndrome will be included in our study. Hemodynamic optimization was performed within 24 hours after diagnosis. After treatment, the patient's heart rate continued to be ≥95 beats/min but ≤120 beats/min for at least 10 minutes, with or without esmolol pumping. The improvement of oxygenation index in different treatment groups was observed.

Being tested
Esmolol
Keywords
esmolol, ARDS, heart rate, oxygenation index
Medical subject headings
Respiratory Distress Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EsmololDrug

    Also called Esmolol hydrochloride injection

    The load dose of esmolol was first injected intravenously: 0.5mg/kg.min, for about 1 minute; then the maintenance dose was pumped intravenously: from 0.05mg/kg/min, and continued after 4 minutes if the efficacy was ideal; if the efficacy was poor, the load dose could be repeated and the maintenance dose increased by 0.05mg/kg/min. The maintenance dose should not exceed 0.3mg/kg/min.

Study groups in NCT06013319
Study groupRoleWhat they receive
Esmolol groupExperimentalPatients with ARDS who require mechanical ventilation after adequate disease assessment and whose heart rate continues to be ≥95 beats/min, but ≤120 beats/min within 24 hours after diagnosis, for at least 10 minutes without changing the dosage of catecholamine, were diagnosed as atrial fibrillation, atrial flutter or sinus tachycardia. The primary treatment is maintained while the esmolol load dose is administered and the maintenance dose is pumped continuously until the patient's heart rate is maintained between 80 and 94 beats per minute.
Receives: Drug: Esmolol
Control groupNo interventionPatients with ARDS who need mechanical ventilation after adequate condition assessment and whose heart rate continues to be ≥95 beats /min but ≤120 beats /min after optimal hemodynamic treatment within 24 hours after diagnosis were randomly included in the control group. Routine mechanical ventilation, full sedation and analgesia, maintain RASS score 0-2 points; The target tidal volume is 6ml/kg, and the ventilator parameters should be adjusted in time according to the blood gas analysis. Hypotensive patients with sufficient blood volume should be pumped with pressor drugs. Timely sputum suction, airway management, eliminate fever, asthma, pain and other stimulation caused by the heart rate is too fast.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Oxygenation index improved or not

    To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.

    Measured: From the start of the trial to 12 hours after administering the drug

  2. Oxygenation index improved or not

    To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.

    Measured: From the start of the trial to 24 hours after administering the drug

  3. Oxygenation index improved or not

    To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.

    Measured: From the start of the trial to 48 hours after administering the drug

  4. Oxygenation index improved or not

    To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.

    Measured: From the start of the trial to 72 hours after administering the drug

  5. Oxygenation index improved or not

    To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.

    Measured: From the start of the trial to 120 hours after administering the drug

Secondary outcomes (1)
  1. the difference of mechanical ventilation duration

    The duration of mechanical ventilation was compared between the two groups with or without esmolol treatment

    Measured: from the start of the trial to removal of the endotracheal tube and cessation of mechanical ventilation,up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2023
  2. Study start20 Feb 2023
  3. Primary completion30 Apr 2026 (estimated)
  4. Study completion30 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
178 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06013319
Sponsor's protocol ID
QFSKYLLTZH-2023-043
Status last verified
Mar 2024
First submitted
22 Aug 2023
Last updated
13 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet. 2021 Aug 14;398(10300):622-637. doi: 10.1016/S0140-6736(21)00439-6. Epub 2021 Jul 1.

    PubMed 34217425
  • van der Jagt M, Miranda DR. Beta-blockers in intensive care medicine: potential benefit in acute brain injury and acute respiratory distress syndrome. Recent Pat Cardiovasc Drug Discov. 2012 Aug;7(2):141-51. doi: 10.2174/157489012801227274.

    PubMed 22642505
  • Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier T, Orecchioni A, D'Egidio A, Cecchini V, Landoni G, Pietropaoli P, Westphal M, Venditti M, Mebazaa A, Singer M. Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study. Crit Care Med. 2013 Sep;41(9):2162-8. doi: 10.1097/CCM.0b013e31828a678d.

    PubMed 23873274
  • Levy B, Fritz C, Piona C, Duarte K, Morelli A, Guerci P, Kimmoun A, Girerd N. Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study. Crit Care. 2021 Jan 7;25(1):21. doi: 10.1186/s13054-020-03445-w.

    PubMed 33413583

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Esmolol in people with Acute Respiratory Distress Syndrome, run by Zhiming Jiang at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Quanzhen Wang, doctor (15562570205, wangquanzhen1986@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Oxygenation index improved or not (time frame: From the start of the trial to 12 hours after administering the drug). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06013319, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.

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