Acute Respiratory Distress SyndromeNCT04641897
Impact of Decreasing Respiratory Rate on Lung Injury Biomarkers in ARDS Patients
A study testing Respiratory rate modification in people with Acute Respiratory Distress Syndrome and Respiration, Artificial, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.
Trial summary
Acute respiratory distress syndrome (ARDS) is a form of acute lung injury of inflammatory origin, which represents a public health problem worldwide due to its prevalence, and its high mortality rate, close to 40%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Respiration, Artificial, Ventilator-Induced Lung Injury
- What is being tested?
- Respiratory rate modification
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChile
- Study dates
- 1 Mar 2020to 1 Feb 2022
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients intubated and under mechanical ventilation with acute respiratory distress syndrome less than 48 hours
- Acute onset (less than 1 week)
- Chest-X-ray: bilateral infiltrates
- Absence of heart failure or hydrostatic pulmonary edema
- Oxygenation disorder: PaO2/FiO2 ratio <200, with PEEP ≥5 cmH2O
Who cannot join
- Age <18 years
- Previous chronic respiratory disease (chronic obstructive lung disease, asthma, intersticial lung disease, pulmonary fibrosis, chronic bronchiectasis)
- Hypercapnic respiratory failure, defined as PaCO2 >60 mmHg or pH<7.25 despite a RR >30.
- Concomitant severe metabolic acidosis: pH<7.20
- Catastrophic respiratory failure, defined as PaO2/FiO2 ratio <80, despite optimization of ventilatory parameters, or need for ECMO.
- Contraindication to hypercapnia, such as intracranial hypertension or acute coronary syndrome
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- Use of vasoconstrictor drugs in increasing doses in the last 2 hours (≥0.5 μg/kg/min of noradrenaline) or average blood pressure <65mmHg
- Pneumothorax or subcutaneous emphysema, not drained.
- Pregnancy
- Presence of mental or intellectual disability prior to hospitalization
- Early limitation of therapeutic effort
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Decreasing Respiratory Rate, While Tolerating Moderate Hypercapnia, on Lung Injury Markers in Patients with Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) is a form of acute lung injury of inflammatory origin, which represents a public health problem worldwide due to its prevalence, and its high mortality rate, close to 40%. Mechanical ventilation is a fundamental therapy to improve gas exchange, however, it can also induce further lung injury, a phenomenon known as ventilator induced lung injury (VILI). The limitation of tidal volume is the strategy that has shown the greatest decrease in mortality and is the cornerstone of protective ventilation. However, the respiratory rate, a fundamental parameter in the programming of the mechanical ventilator, has not been evaluated in most of the main clinical studies to date. Moreover, the natural clinical response to the use of a low tidal volume strategy is the increase in respiratory rate, which may harm the lung as it increases the energy applied to the lung parenchyma. The investigators hypothesize that the use of a lower respiratory rate, tolerating moderate hypercapnia, is associated with less VILI, measured by the release of proinflammatory mediators at the systemic level (biotrauma), compared to a conventional higher respiratory rate strategy in patients with moderate to severe ARDS. This effect is mediated by lower energy applied to the pulmonary parenchyma. To confirm this hypothesis the investigators propose a prospective cross-over clinical trial in 30 adult patients with ARDS in its acute phase, which will be randomized to two sequences of ventilation. Each period will last 12 hours, and respiratory rate (RR) will be set according to PaCO2 goal: 1) Low RR, PaCO2 60-70 mmHg; and 2) High RR, PaCO2 35-40 mmHg.
Protective ventilation will be applied according to ICU standards under continuous sedation and neuromuscular blockade. Invasive systemic arterial pressure and extravascular lung water will be monitored through an arterial catheter (PICCO® system), and airway and esophageal pressures and hemodynamics continuously measured throughout the protocol. The main outcome will be Interleukin-6 in plasma. At baseline and at the end of each period blood samples will be taken for analysis, and electrical impedance tomography (EIT) and transthoracic echocardiography will be registered. After the protocol, patients will continue their management according to ICU standards.
- Conditions
- Acute Respiratory Distress Syndrome, Respiration, Artificial, Ventilator-Induced Lung Injury
- Being tested
- Respiratory rate modification
- Keywords
- Respiratory rate, Mechanical ventilation, ARDS, Ventilator induced lung injury
- Medical subject headings
- Respiratory Distress Syndrome, Respiratory Aspiration, Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Respiratory rate modificationProcedure or surgery
During the Low RR and High RR periods, respiratory rate will be set depending on baseline ABG and according a nomogram so as to have an approximate difference of 10 points between groups, while maintining PaCO2 and pH values within safety limits (pH 7.20 to 7.45, and PaCO2 35 to 60 mmHg).
Once defined the target respiratory rate, this will be decreased or increased in 4 points each 30 to 45 min, and ABG repeated at 2 hours. At this time, changes will be made to keep PaCO2 and pH values within safety limits, and ABG repeated at 6 and finally 12 hours.
During the whole period, inspiratory to expiratory ratio will be maintained constant, and only changed to keep inspiratory time above 0.6 seconds (usually at high resp rate).
| Study group | Role | What they receive |
|---|---|---|
| Sequence A | Other | Sequence A: Low RR for 12 hours - High RR for 12 hours Receives: Procedure: Respiratory rate modification |
| Sequence B | Other | Sequence B: High RR for 12 hours - Low RR for 12 hours. Receives: Procedure: Respiratory rate modification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in IL-6
levels of IL-6 in plasma
Measured: baseline, 12 and 24 hours
Secondary outcomes (8)
Changes in transpulmonary driving pressures
Measured: Baseline, 12 and 24 hours
Changes in Auto PEEP
Measured: Baseline, 12 and 24 hours
Changes in mean airway pressure
Measured: Baseline, 12 and 24 hours
Changes in level of energy applied to the lungs
Measured: Baseline, 12 and 24 hours
Changes in arterials blood gases
Measured: Baseline, 12 and 24 hours
Changes overtime in distribution of ventilation
Distribution of ventilation as assessed by Electrical impedance tomography
Measured: Baseline, 6,12, 24 hours
Changes in cardiac function and pulmonary edema
measured by PICCO®.
Measured: Baseline, 12 and 24 hours
Changes pulmonary edema
measured by PICCO®.
Measured: Baseline, 12 and 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2020
- Study start1 Mar 2020
- Primary completion1 Feb 2022
- Study completion1 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Pontificia Universidad Catolica de ChileThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pontificia Universidad Catolica de Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04641897
- Sponsor's protocol ID
- 180813016
- Other IDs
- 1191315
- Status last verified
- Nov 2020
- First submitted
- 9 Oct 2020
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Damiani LF, Basoalto R, Oviedo V, Alegria L, Soto D, Bachmann MC, Jalil Y, Santis C, Carpio D, Ulloa R, Valenzuela D, Vera M, Schultz MJ, Retamal J, Bruhn A, Bugedo G. Effect of decreasing respiratory rate on the mechanical power of ventilation and lung injury biomarkers: a randomized cross-over clinical study in COVID-19 ARDS patients. Intensive Care Med Exp. 2025 Jul 9;13(1):69. doi: 10.1186/s40635-025-00782-4.
PubMed 40632387
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Decreasing Respiratory Rate, While Tolerating Moderate Hypercapnia, on Lung Injury Markers in Patients with Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04641897
- Acronym / sponsor ID
- 180813016
- Conditions
- Acute Respiratory Distress Syndrome, Respiration, Artificial, Ventilator-Induced Lung Injury
- Keywords
- Respiratory rate, Mechanical ventilation, ARDS, Ventilator induced lung injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Pontificia Universidad Catolica de ChileUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 Feb 2022 (actual)
- Study completion
- 1 Feb 2022 (actual)
- First posted
- 24 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute respiratory distress syndrome (ARDS) is a form of acute lung injury of inflammatory origin, which represents a public health problem worldwide due to its prevalence, and its high mortality rate, close to 40%. Mechanical ventilation is a fundamental therapy to improve gas exchange, however, it can also induce further lung injury, a phenomenon known as ventilator induced lung injury (VILI). The limitation of tidal volume is the strategy that has shown the greatest decrease in mortality and is the cornerstone of protective ventilation. However, the respiratory rate, a fundamental parameter in the programming of the mechanical ventilator, has not been evaluated in most of the main clinical studies to date. Moreover, the natural clinical response to the use of a low tidal volume strategy is the increase in respiratory rate, which may harm the lung as it increases the energy applied to the lung parenchyma. The investigators hypothesize that the use of a lower respiratory rate, tolerating moderate hypercapnia, is associated with less VILI, measured by the release of proinflammatory mediators at the systemic level (biotrauma), compared to a conventional higher respiratory rate strategy in patients with moderate to severe ARDS. This effect is mediated by lower energy applied to the pulmonary parenchyma. To confirm this hypothesis the investigators propose a prospective cross-over clinical trial in 30 adult patients with ARDS in its acute phase, which will be randomized to two sequences of ventilation. Each period will last 12 hours, and respiratory rate (RR) will be set according to PaCO2 goal: 1) Low RR, PaCO2 60-70 mmHg; and 2) High RR, PaCO2 35-40 mmHg.
Protective ventilation will be applied according to ICU standards under continuous sedation and neuromuscular blockade. Invasive systemic arterial pressure and extravascular lung water will be monitored through an arterial catheter (PICCO® system), and airway and esophageal pressures and hemodynamics continuously measured throughout the protocol. The main outcome will be Interleukin-6 in plasma. At baseline and at the end of each period blood samples will be taken for analysis, and electrical impedance tomography (EIT) and transthoracic echocardiography will be registered. After the protocol, patients will continue their management according to ICU standards.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A | Other | Procedure: Respiratory rate modificationSequence A: Low RR for 12 hours - High RR for 12 hours |
| Sequence B | Other | Procedure: Respiratory rate modificationSequence B: High RR for 12 hours - Low RR for 12 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients intubated and under mechanical ventilation with acute respiratory distress syndrome less than 48 hours
- Acute onset (less than 1 week)
- Chest-X-ray: bilateral infiltrates
- Absence of heart failure or hydrostatic pulmonary edema
- Oxygenation disorder: PaO2/FiO2 ratio <200, with PEEP ≥5 cmH2O
Key exclusion criteria (11 listed)
- Age <18 years
- Previous chronic respiratory disease (chronic obstructive lung disease, asthma, intersticial lung disease, pulmonary fibrosis, chronic bronchiectasis)
- Hypercapnic respiratory failure, defined as PaCO2 >60 mmHg or pH<7.25 despite a RR >30.
- Concomitant severe metabolic acidosis: pH<7.20
- Catastrophic respiratory failure, defined as PaO2/FiO2 ratio <80, despite optimization of ventilatory parameters, or need for ECMO.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Respiratory rate modificationDuring the Low RR and High RR periods, respiratory rate will be set depending on baseline ABG and according a nomogram so as to have an approximate difference of 10 points between groups, while maintining PaCO2 and pH values within safety limits (pH 7.20 to 7.45, and PaCO2 35 to 60 mmHg). Once defined the target respiratory rate, this will be decreased or increased in 4 points each 30 to 45 min, and ABG repeated at 2 hours. At this time, changes will be made to keep PaCO2 and pH values within safety limits, and ABG repeated at 6 and finally 12 hours. During the whole period, inspiratory to expiratory ratio will be maintained constant, and only changed to keep inspiratory time above 0.6 seconds (usually at high resp rate). | Procedure or surgery | Sequence A, Sequence B |
Primary outcome
Changes in IL-6
Time frame: baseline, 12 and 24 hours
levels of IL-6 in plasma
8 secondary outcomes
Changes in transpulmonary driving pressures
Time frame: Baseline, 12 and 24 hours
Changes in Auto PEEP
Time frame: Baseline, 12 and 24 hours
Changes in mean airway pressure
Time frame: Baseline, 12 and 24 hours
Changes in level of energy applied to the lungs
Time frame: Baseline, 12 and 24 hours
Changes in arterials blood gases
Time frame: Baseline, 12 and 24 hours
Changes overtime in distribution of ventilation
Time frame: Baseline, 6,12, 24 hours
Changes in cardiac function and pulmonary edema
Time frame: Baseline, 12 and 24 hours
Changes pulmonary edema
Time frame: Baseline, 12 and 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Derived from this study: PubMed 40632387Damiani LF, Basoalto R, Oviedo V, Alegria L, Soto D, Bachmann MC, Jalil Y, Santis C, Carpio D, Ulloa R, Valenzuela D, Vera M, Schultz MJ, Retamal J, Bruhn A, Bugedo G. Effect of decreasing respiratory rate on the mechanical power of ventilation and lung injury biomarkers: a randomized cross-over clinical study in COVID-19 ARDS patients. Intensive Care Med Exp. 2025 Jul 9;13(1):69. doi: 10.1186/s40635-025-00782-4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Respiratory rate modification in people with Acute Respiratory Distress Syndrome and Respiration, Artificial, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.
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 11 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: finished, as of the sponsor's last update on 13 Jan 2025. 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 Chile. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in IL-6 (time frame: baseline, 12 and 24 hours). 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 NCT04641897, which also lists 1 linked publication.
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 Jan 2025.