Acute Hypoxemic Respiratory FailurePhase 3NCT00924846
High-Frequency Oscillatory Ventilation Associated With Inhaled Nitric Oxide in Children
A Phase 3 study testing High frequency oscillatory ventilation in people with Acute Hypoxemic Respiratory Failure, run by UPECLIN HC FM Botucatu Unesp at 1 site in Brazil.
Trial summary
Background/Objectives: Acute hypoxemic respiratory failure (AHRF) is a frequent cause of pediatric ICU admission. Early treatment with inhaled nitric oxide (iNO) plus conventional mechanical ventilation (CMV) improves oxygenation, responsiveness being significantly influenced by alveolar recruitment level. Read more about this study
- Who is it for?
- Ages 1 month to 14 years
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure
- What is being tested?
- High frequency oscillatory ventilation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteBrazil
- Study dates
- Apr 2005to Jun 2009
- 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 1 month to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children with AHRF (oxygenation index ≥ 10) aged between one month and 14 years under CMV with PEEP ≥ 10 cmH2O and 5 ppm iNO for 1 hour.
Who cannot join
- Children with chronic cardiac or pulmonary diseases.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: High-Frequency Oscillatory Ventilation Associated With Inhaled Nitric Oxide in Children: Randomized, Crossover Study
Background/Objectives: Acute hypoxemic respiratory failure (AHRF) is a frequent cause of pediatric ICU admission. Early treatment with inhaled nitric oxide (iNO) plus conventional mechanical ventilation (CMV) improves oxygenation, responsiveness being significantly influenced by alveolar recruitment level. High-frequency oscillatory ventilation (HFV) is conceptually very attractive as constant mean airway pressure optimizes lung recruitment; this could maximize iNO effects.
Aims: To analyze the effects of HFV on oxygenation indexes in AHRF children under CMV and iNO.
Methods: Children with AHRF (oxygenation index ≥10) aged between one month and 14 years under CMV with PEEP≥10cmH2O and 5ppm iNO for 1h were randomly assigned to CMV (CMVG, n=12) or HFV (HFVG, n=12) in a crossover design. Children with chronic cardiac or pulmonary diseases were excluded. Patients were kept under one of the two ventilation modes for 8h, crossing to the other for 8h, and then back again to complete 24h observation. Blood gas analysis, oxygenation indexes, and hemodynamic variables were recorded at enrollment (Tind), 1h after iNO start and then every 4h (T4h etc). The Mann-Whitney U test compared group ages and PRISM scores, and the Fisher test genders. Moments and groups were compared by repeated measure analysis for independent groups. Significance was considered at p<0.05.
Read the detailed description
Acute hypoxemic respiratory failure (AHRF) is a frequent cause of admission and complicates evolution of critically ill children. Mortality rate is still high, mainly when acute respiratory distress syndrome (ARDS) evolves.
Clinical management of AHRF is essentially supportive and includes control of underlying infections, fluid balance and hemodynamic status, nutritional support, and optimized protective mechanical ventilation4,5,6. Ventilatory strategies should be directed at minimizing ventilator-induced lung injury (VILI), eliminating oxygen toxicity, and controlling lung inflammation. Also, when hypoxemia persists, additional treatments may be implemented, such as inhaled nitric oxide (iNO)and high-frequency oscillatory ventilation (HFOV).
Recently, we have demonstrated that early treatment with iNO associated with protective conventional mechanical ventilation (CMV) causes acute and sustained improvement in oxygenation, with earlier reduction in ventilator settings that are associated with a high risk of VILI and oxygen toxicity; this might contribute to reducing the mortality rate in children with ARDS.
However, many studies have given no value to iNO therapy because of a lack of impact on mortality rate. Despite this, it should be considered that the improvement in oxygenation promoted by NO inhalation may be useful as rescue therapy. Also, it is known that responsiveness to iNO can be significantly influenced by applying sufficient positive and expiratory pressure (PEEP), as this seems to recruit additional alveoli for gas exchange. In this sense, HFOV is very attractive as the application of a constant mean airway pressure maintains an "open lung" and optimizes lung recruitment; this could maximize iNO effects.
Two experimental studies have shown increased iNO effects when the gas was used together with HFOV. In ARDS adults, Authors studied this association and demonstrated improvement in oxygenation with significant reduction in FiO2, probably due to the degree of alveolar recruitment during HFOV which may increase the amount of alveolar/capillary interface available for iNO to act upon.
In pediatrics, there is one study combining iNO and HFOV in newborn babies with severe persistent pulmonary hypertension which concluded that the association is often more successful than each treatment alone23. After neonatal period, a retrospective (post hoc) data analysis from a multicenter, randomized controlled trial on the effects of iNO in the treatment of AHRF concluded that the combination of HFOV with iNO causes greater improvement in oxygenation than either treatment strategy alone.
Therefore, the question about the potential role of the association between iNO therapy and HFOV in AHRF children is still open and remains to be defined. Our hypothesis is the association between early iNO treatment and HFOV improves oxygenation more consistently and for longer time than the association of the gas with protective conventional mechanical ventilation.
The aim of this study was to analyze the effects of HFOV on oxygenation indexes in AHRF children under CMV and iNO therapy.
- Conditions
- Acute Hypoxemic Respiratory Failure
- Being tested
- High frequency oscillatory ventilation
- Keywords
- high frequency oscillatory ventilation, respiratory failure, children, inhaled nitric oxide
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High frequency oscillatory ventilationProcedure or surgery
Also called HFOV
Mechanical ventilation as high frequency oscillatory ventilation for 8h periods
| Study group | Role | What they receive |
|---|---|---|
| HFOV plus iNO | Active comparator | HFOV plus iNO: high frequency oscillatory ventilation plus inhaled nitric oxide Receives: Procedure: High frequency oscillatory ventilation |
| CMV plus iNO | Active comparator | CMV (conventional mechanical ventilation) iNO (inhaled nitric oxide) Receives: Procedure: High frequency oscillatory ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxygenation indexes
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2009 (estimated)
- Study startApr 2005
- Primary completionApr 2008
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- UPECLIN HC FM Botucatu Unesp
- Sponsor type
- University, hospital or other
- Investigators
- Jose R Fioretto, MD, PhD, Study chair, UNESP-Botucatu Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00924846
- Sponsor's protocol ID
- upeclin/HC/FMB-Unesp-26
- Status last verified
- Jun 2009
- First submitted
- 18 Jun 2009
- Last updated
- 22 Jun 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Frequency Oscillatory Ventilation Associated With Inhaled Nitric Oxide in Children: Randomized, Crossover Study
- ClinicalTrials.gov ID
- NCT00924846
- Acronym / sponsor ID
- upeclin/HC/FMB-Unesp-26
- Conditions
- Acute Hypoxemic Respiratory Failure
- Keywords
- high frequency oscillatory ventilation, respiratory failure, children, inhaled nitric oxide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- UPECLIN HC FM Botucatu UnespUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- Apr 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 19 Jun 2009 (estimated)
- 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.
Background/Objectives: Acute hypoxemic respiratory failure (AHRF) is a frequent cause of pediatric ICU admission. Early treatment with inhaled nitric oxide (iNO) plus conventional mechanical ventilation (CMV) improves oxygenation, responsiveness being significantly influenced by alveolar recruitment level. High-frequency oscillatory ventilation (HFV) is conceptually very attractive as constant mean airway pressure optimizes lung recruitment; this could maximize iNO effects.
Aims: To analyze the effects of HFV on oxygenation indexes in AHRF children under CMV and iNO.
Methods: Children with AHRF (oxygenation index ≥10) aged between one month and 14 years under CMV with PEEP≥10cmH2O and 5ppm iNO for 1h were randomly assigned to CMV (CMVG, n=12) or HFV (HFVG, n=12) in a crossover design. Children with chronic cardiac or pulmonary diseases were excluded. Patients were kept under one of the two ventilation modes for 8h, crossing to the other for 8h, and then back again to complete 24h observation. Blood gas analysis, oxygenation indexes, and hemodynamic variables were recorded at enrollment (Tind), 1h after iNO start and then every 4h (T4h etc). The Mann-Whitney U test compared group ages and PRISM scores, and the Fisher test genders. Moments and groups were compared by repeated measure analysis for independent groups. Significance was considered at p<0.05.
Detailed description
Acute hypoxemic respiratory failure (AHRF) is a frequent cause of admission and complicates evolution of critically ill children. Mortality rate is still high, mainly when acute respiratory distress syndrome (ARDS) evolves.
Clinical management of AHRF is essentially supportive and includes control of underlying infections, fluid balance and hemodynamic status, nutritional support, and optimized protective mechanical ventilation4,5,6. Ventilatory strategies should be directed at minimizing ventilator-induced lung injury (VILI), eliminating oxygen toxicity, and controlling lung inflammation. Also, when hypoxemia persists, additional treatments may be implemented, such as inhaled nitric oxide (iNO)and high-frequency oscillatory ventilation (HFOV).
Recently, we have demonstrated that early treatment with iNO associated with protective conventional mechanical ventilation (CMV) causes acute and sustained improvement in oxygenation, with earlier reduction in ventilator settings that are associated with a high risk of VILI and oxygen toxicity; this might contribute to reducing the mortality rate in children with ARDS.
However, many studies have given no value to iNO therapy because of a lack of impact on mortality rate. Despite this, it should be considered that the improvement in oxygenation promoted by NO inhalation may be useful as rescue therapy. Also, it is known that responsiveness to iNO can be significantly influenced by applying sufficient positive and expiratory pressure (PEEP), as this seems to recruit additional alveoli for gas exchange. In this sense, HFOV is very attractive as the application of a constant mean airway pressure maintains an "open lung" and optimizes lung recruitment; this could maximize iNO effects.
Two experimental studies have shown increased iNO effects when the gas was used together with HFOV. In ARDS adults, Authors studied this association and demonstrated improvement in oxygenation with significant reduction in FiO2, probably due to the degree of alveolar recruitment during HFOV which may increase the amount of alveolar/capillary interface available for iNO to act upon.
In pediatrics, there is one study combining iNO and HFOV in newborn babies with severe persistent pulmonary hypertension which concluded that the association is often more successful than each treatment alone23. After neonatal period, a retrospective (post hoc) data analysis from a multicenter, randomized controlled trial on the effects of iNO in the treatment of AHRF concluded that the combination of HFOV with iNO causes greater improvement in oxygenation than either treatment strategy alone.
Therefore, the question about the potential role of the association between iNO therapy and HFOV in AHRF children is still open and remains to be defined. Our hypothesis is the association between early iNO treatment and HFOV improves oxygenation more consistently and for longer time than the association of the gas with protective conventional mechanical ventilation.
The aim of this study was to analyze the effects of HFOV on oxygenation indexes in AHRF children under CMV and iNO therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HFOV plus iNO | Active comparator | Procedure: High frequency oscillatory ventilationHFOV plus iNO: high frequency oscillatory ventilation plus inhaled nitric oxide |
| CMV plus iNO | Active comparator | Procedure: High frequency oscillatory ventilationCMV (conventional mechanical ventilation) iNO (inhaled nitric oxide) |
Who may qualify
- Ages
- 1 month to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Children with AHRF (oxygenation index ≥ 10) aged between one month and 14 years under CMV with PEEP ≥ 10 cmH2O and 5 ppm iNO for 1 hour.
Key exclusion criteria (1 listed)
- Children with chronic cardiac or pulmonary diseases.
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 |
|---|---|---|
| High frequency oscillatory ventilationAlso: HFOVMechanical ventilation as high frequency oscillatory ventilation for 8h periods | Procedure or surgery | CMV plus iNO, HFOV plus iNO |
Primary outcome
Oxygenation indexes
Time frame: 2 years
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 22 Jun 2009.
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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.
Jose R Fioretto, MD, PhD study chair
UNESP-Botucatu Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing High frequency oscillatory ventilation in people with Acute Hypoxemic Respiratory Failure, run by UPECLIN HC FM Botucatu Unesp at 1 site in Brazil.
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 1 inclusion and 1 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 22 Jun 2009. 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 Brazil. 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?
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?
Oxygenation indexes (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jun 2009.