An interventional study of High Flow Nasal Cannula Oxygenation and Venturi Mask Oxygenation in Respiratory Insufficiency and Pneumonia, sponsored by Papa Giovanni XXIII Hospital. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-07.
Sponsored by Papa Giovanni XXIII Hospital · Not applicable, Interventional, and Treatment
The primary objective of this study is to compare the efficacy of treatment with HFNC (group A) compared to administration of oxygen therapy by Venturi mask (group B, standard therapy) in terms of reaching of endotracheal intubation criteria during acute respiratory failure due to severe pneumonia.
Inclusion Criteria: Respiratory rate (RR) at rest ≥20 bpm or presence of respiratory distress (severe dyspnoea at rest or use of accessory respiratory muscles or abdominal paradox); PaO2 / FiO2 ≤250 during oxygenation with Venturi Oxygenation mask at FiO2 = 50% administered for at least 60 minutes; Diagnosis of pneumonia as the sole cause of acute respiratory failure. Randomization: 150 consecutive patients will be randomized either to High Flow Nasal Cannula Oxygenation (75 patients, HFNCO with flow ≥ 60 L/min and FiO2 to maintain SpO2 ≥ ) or Venturi Mask Oxygenation (control, 75 patients).
Patients from both groups will be treated with antibiotic therapy according to the IDSA/ATS 2007 guidelines for community-acquired pneumonia and the IDSA/ATS 2016 guidelines for hospital-acquired pneumonia.
Intubation Criteria:
MAJOR CRITERIA:
Cardiac or respiratory arrest Breathing pauses with loss of consciousness Severe hemodynamic instability Need for sedation
MINOR CRITERIA (maintained for ≥1h):
Reduction ≥30% of the value of the PaO2/FiO 2 compared to baseline Increased 20% if PaCO2 PaCO2 previous ≥40mmHg Worsening alertness as increased by one degree on the Kelly scale Persistence or onset of respiratory distress Vital parameters, Kelly scale and arterial blood gas analysis (BGA) will be performed on admission, and at 1, 24, at 48 hours, at the achievement of clinical stability, and whenever there is a clinical worsening.
Patients enrolled in HFNC arm will continue HFNC oxygenation until clinical stability, defined as:
Body temperature ≤ 37°C and ≥36°C for 24 consecutive hours Good ability in swallowing CRP and WBC normalization trend than the admission exams Hemodynamic stability Lack of respiratory distress SpO2 94-98% The primary outcome variable is the proportion of patients who reach the endotracheal intubation criteria - regardless of the actual intubation rate - within the first 48 hours of treatment. The primary analysis will be performed on the ITT population
1.1 Basic information Pneumonia is still the most important infectious disease in terms of morbidity and mortality and is one of the most common causes of hospitalization for acute respiratory failure. The aim of this trial is to compare the use of High Flow Nasal Cannula (HFNC) oxygenation versus standard oxygen therapy in patients with hypoxemia due to pneumonia.
1.2 Rationale The oxygenation through HFNC allows the use of high concentrations of oxygen administered by a high gas flow, heated and humidified. This device allows both higher FiO2 and the presence of a positive end-expiratory pressure (PEEP) with a greater gas exchange.
The secondary aims are:
30-day mortality gas exchange improvement in-hospital length of stay adverse events as per prior
3.3 Duration of the study The estimated time to complete the recruitment of cases is 24 months. Each subject will be followed from enrolment until discharge.
3.4 Evaluation 3.5.1 Primary endpoint The primary endpoint is the achievement of clinical failure defined as at least one major criteria Or
At least ≥2 of the minor criteria maintained for at least 1 consecutive hour:
MAJOR CRITERIA:
Cardiac or respiratory arrest Breathing pauses with loss of consciousness Severe hemodynamic instability Need for sedation
MINOR CRITERIA:
Reduction ≥30% of the value of the PaO 2 / FiO 2 compared to baseline Increased 20% if PaCO2 PaCO2 previous ≥40mmHg Worsening alertness as increased by one degree on the Kelly scale Persistence or onset of respiratory distress
3.5.2 Secondary endpoint
The secondary endpoint includes:
30 days mortality after admission. improvement of respiratory exchanges compared to baseline, rated at 1, 24 and 48 hours and at the achievement of clinical stability with arterial blood gas.
rate of adverse events length of hospital stay. 3.5.3 Follow-up At 30 days from admission, each subject will be assessed, possibly through telephone contact, to determine the status of life (secondary endpoint).
5.2 Masking This study is open, not being justified a possible double masking technique or sham procedures.
6.1 Clinical evaluation
Clinical evaluations include:
collection of history (prior and concomitant diseases), and any concomitant therapies complete physical exam only at baseline respiratory symptoms at each evaluation vital signs during each evaluation dyspnea assessment at every clinical evaluation, using the Borg scale axillary body temperature (BT) every 8 hours Kelly scale assessment at each evaluation.
6.2 Laboratory evaluations Unless otherwise specified, the following tests will be performed on admission, 24 hours and then every 48 hours until discharge criteria are reached.
CBC: (5 mL in EDTA); Biochemistry: blood urea nitrogen, creatinine, serum sodium, potassium, glucose, ALT, AST, creatine phosphokinase (CPK), bilirubin, C-reactive protein, albumin (5 mL whole blood); lactates: performed at baseline and subsequent blood gas controls (3 mL of whole blood) pregnancy test on the urine sample (only at baseline) The arterial blood gas analysis (BGA) with the calculation of PaO2/FiO2 will be performed on admission, at 1, 24, at 48 hours, and at the achievement of clinical stability, and whenever there is a clinical worsening.
6.3 Instrumental exams Routine chest x-ray on admission, as well as whenever a clinical deterioration occurs.
6.4 Examinations plan 6.4.1 Baseline medical exam For each patient it will be made physical examination and lab evaluation as described previously Then it will proceed to randomization as indicated in § 5.2. 6.4.2 Treatment period The doctor in charge is free to perform all measurements, including BGA, as needed to assess the patient's condition. These will be in the clinic folder but they are not part of the data analyzed for the study, with the exception of blood gas analysis necessary to determine the minor intubation criteria (§ 3.5.1). Such measures will be noted for determination of primary endpoint, but they will not be used for the measurement of gas exchange trend (secondary endpoint).
For the analysis of secondary endpoint, after 24 hours, 48 hours and the achievement of clinical stability should be measured and recorded:
vital parameters (BP, HR, RR). The BT is measured every 8 hours with other vital parameters evaluation of dyspnea using both the Borg scale and the Kelly scale adverse events BGA during the treatment with lactate measurement (maintaining the HFNC and oxygen therapy with a mask as defined for randomization) and evaluation of P/F ratio, A-a difference of O2 and arterial O2 consumption.
24 hours after randomization there will be rated the severity score the SAPS-II scale and the SOFA score in case of sepsis.
Every 48 hours there will be performed blood samples (CBC, biochemistry, CRP) until the clinical stability is reached.
If intubation criteria are reached, the study must be regarded as concluded. For patients enrolled in HFNC arm, the ventilatory support therapy using HFNC must be continued until the clinical stability, considered as the fulfillment of the following clinical stability.
After attainment of all clinical stability, there will be an attempt to remove HFNC and to put the patient in Venturi mask, with the same FiO2 as the HFNC used before.
This step will be considered definitive when one hour after the attempt the SpO2 remains 94-98% and the absence of respiratory distress or FR \<25 acts per minutes.
For patients in Venturi group, as soon as clinical stability is reached through the fulfillment of clinical stability criteria, the successive evaluation takes place at the time of discharge.
6.4.3 End-study medical examination The visit will take place at the end of the study at the time of discharge or when intubation criteria will be achieved.
Evaluation will include:
vital parameters (BP, HR, RR) respiratory symptoms using both the Borg and the Kelly scale SpO2 6.4.4 Observations to 30 days or in case of unplanned evaluation
After 30 days of enrolment the patient will be requested via telephone interview of the subject or of the reference family:
If the participant is alive any hospitalization
9.2 Study design The study follows the randomized, controlled design vs. standard open intervention. Randomization is defined by the main statistician. The center receives a set of disposable sealed envelopes, opaque, prepared by the main statistician in blocks in accordance with procedures stored by itself. Each subject enrolled will receive the treatment indicated inside the envelope with the lowest number available.
9.3 Outcome measures of the study See appropriate section on Outcome Measures
9.4 Study hypothesis The study aims to evaluate the null hypothesis according to the proportion of patients reaching the primary endpoint does not differ in its populations.
9.5 Sample size The aim of the study is the null hypothesis examination, which indicates that the groups in the two populations are the same.
With the proposed sample of 75 subjects in both the two groups (a total of 150 subjects), the study has a power of 80% to give statistically significant results. This calculation assumes that the proportion of subjects that reach the primary endpoint is approximately the 60% of the control group and that the treatment in question is able to reduce this proportion of 35%.
9.6 Patients enrolling and follow-up Overall, it is expected to enrol approximately 150 patients. The estimated duration of enrolment is about 12 months. Considering the period of follow up of the patients, the expected study duration is approximately 36 months.
9.7 Analysis plan 9.7.1 Primary variable analysis The primary variable is the proportion of patients who meet the criteria for endotracheal intubation - regardless of the actual intubation - during the treatment until the achievement of the clinical stability criteria. The primary analysis will be performed on the ITT population. The proportion of subjects qualified as a "failure" related to the achievement of the criteria for intubation will be analyzed by contingency tables (chi-square) accompanied by the confidence interval of the difference, by the relative risk estimates and by the NNT, if applicable. It may also be analyzed by multivariate logistic regression.
The proportion of subjects who achieved the outcome at a set time (secondary analysis), if relevant, will be tabulated by relative confidence intervals for the difference and estimated odds-ratios for daily intervals.
9.7.2 Secondary variables analysis The Secondary endpoints include both continuous and binary distribution variables. The 30-day mortality will be analyzed by contingency tables and using multivariate logistic regression, considering as membership population these three categories: HFNC, Venturi (if randomized to standard after treatment maintained until the end of observation) and Mixed (if randomized to standard treatment and subsequently transferred to HFNC before the observation term)
1,369 studies on the registry are indexed under Respiratory Insufficiency; 264 are open to participants now.
This study's planned enrollment of 150 is above the median of 60 across 860 interventional studies indexed under Respiratory Insufficiency.
Browse Respiratory Insufficiency studies →Papa Giovanni XXIII Hospital is the lead sponsor of 22 studies on the registry; 6 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
High Flow Nasal Cannula Oxygenation with a minimum flow ≥ 60L / min, and an FiO2 such as to maintain a SpO2 ≥ 92% for at least 48 hours until clinical stability
Device: High Flow Nasal Cannula Oxygenation
Venturi Mask Oxygenation, with an FiO2 such as to maintain an SpO2 ≥ 92% for at least 48 hours until clinical stability
Device: Venturi Mask Oxygenation
Delivery of humidified and heated (37ºC) high flow oxygen
delivery of high flow oxygen
Clinical Failure
The primary endpoint is the achievement of clinical failure defined as: At least one of major criteria Or At least 2 or more of the minor criteria maintained for at least 1 consecutive hour: MAJOR CRITERIA: Cardiac or respiratory arrest Breathing pauses with loss of consciousness Severe hemodynamic instability (Heart Rate ≤ 50 bpm with loss of alertness or Systolic Blood Pressure ≤ 70 mmHg) Need for sedation MINOR CRITERIA (observed for ≥ 1 hour): Reduction ≥30% of the value of the PaO 2 / FiO 2 compared to baseline Increased 20% if PaCO2 PaCO2 previous ≥40mmHg Worsening alertness as increased by one degree on the Kelly scale (see Appendix II) Persistence or onset of respiratory distress ( severe dyspnea or use of accessories respiratory muscles or paradoxical abdominal motion)
Time frame: Participants will be followed for the duration of hospital stay, for a maximum of 30 days
30-day mortality after admission
mortality rate at 30 days after admission
Time frame: day 30
improvement of respiratory exchanges compared to baseline
arterial blood gas evaluation of gas exchange and ventilation
Time frame: hospital admission (=day 1), day 2, until the achievement of clinical stability
adverse events
observation adverse events rate
Time frame: Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week
hospital stay
length of hospital stay
Time frame: Hospital discharge; participants will be followed for the duration of hospital stay, an expected average of 1 week
Plan to share: No
Started Jun 2023 (actual). Primary completion is estimated for Dec 2025, 30 months after the start.
Of 359 non-industry interventional studies with no phase under Respiratory Insufficiency, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 11 and three quarters within 47. This study's planned 30 months is above that.
Counting every sponsor, half of 375 studies reached it within 24 months; a quarter within 10 and three quarters within 46.
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Papa Giovanni XXIII Hospital