Lung DiseasePhase 3NCT02191410
Nondependent Lung Ventilation and Fluid Responsiveness
A Phase 3 study testing High Frequency Positive Pressure Ventilation and Continuous Positive Airway Pressure in people with Lung Disease and Undergoing Thoracosocpic Surgery, run by Imam Abdulrahman Bin Faisal University at 1 site in Saudi Arabia.
Trial summary
The stroke volume variation (SVV), measured using the Vigileo-FloTrac system (Edwards Lifescience, Irvine, CA), has been shown to able to predict fluid responsiveness during one-lung ventilation (OLV) in patients undergoing pulmonary lobectomy (sensitivity: 82.4%, specificity: 92.3%).1 Many parameters such as tidal… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Lung Disease, Undergoing Thoracosocpic Surgery
- What is being tested?
- High Frequency Positive Pressure Ventilation and Continuous Positive Airway Pressure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteSaudi Arabia
- Study dates
- Jan 2019to Jun 2020
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- American Society of Anesthesiologists physical class of II to III
- Duration of OLV is expected to exceed 1.5 hours
Who cannot join
- New York Heart Association class > II
- Right ventricular dysfunction
- Pulmonary hypertension
- valvular heart disease
- intracardiac shunts
- Any cardiac rhythm other than sinus
Show all 14Show fewer
- Hypertension
- Diabetes mellitus
- Renal dysfunction
- Hepatic dysfunction
- Pregnancy
- Body mass index >35 kg m-2
- Peripheral arterial occlusive disease
- preoperative administration of inotropic medications
Trial locations and contacts
1 site in 1 country.
Saudi Arabia1 site
King Fahd Hospital of the University
Khobar, Eastern Province, 31952
Abdulmohsen A Al Ghamdi, MD, +966 13 8966666 ext. 2021, mohsenkfu@hotmail.com
Mohamed R El Tahan, MD
About this study
Official title: Comparative Study of the Non-dependent Continuous Positive Airway Pressure and High-frequency Positive-pressure Ventilation on Fluid Responsiveness During One-lung Ventilation for Thoracoscopic Surgery
The stroke volume variation (SVV), measured using the Vigileo-FloTrac system (Edwards Lifescience, Irvine, CA), has been shown to able to predict fluid responsiveness during one-lung ventilation (OLV) in patients undergoing pulmonary lobectomy (sensitivity: 82.4%, specificity: 92.3%).1 Many parameters such as tidal volume (TV),1-2 positive end-expiratory pressure (PEEP),3 respiratory rate (RR), 4 chest and lung compliance,5 heart rate and rhythm, and ventricular function and afterload,6-7 all have been documented to have effects on the SVV.
SVV is calculated as the variation of beat-to-beat SV from the mean value during the most recent 20 seconds of data: SVV = (SVmax - SVmin)/SVmean, where SVmax, SVmin, and SVmean are, respectively, the maximum, minimum, and mean SV determined by the system.
Read more
SVV may not be sufficiently sensitive to predict fluid responsiveness in patients with right ventricular (RV) dysfunction due to concomitant increases in RV afterload, that lead to a decrease in preload variation and subsequent inaccuracy in SVV measurements.8
OLV may increase airway pressure, resulting in increases in the RV afterload, end-diastolic volume, and stroke work index, thus impeding RV function.9-11The increases in the right ventricular afterload may exaggerate the cyclic variation in stroke volume.12
In the authors' previous study,9 they found that the high-frequency positive-pressure ventilation (HFPPV) was superior to continuous positive-airway pressure (CPAP) for OLV, resulting in significantly higher RV ejection fraction, lower RV afterload and higher arterial oxygenation, whereas the former limiting the adequate operative field visualization during video-assisted thoracoscopic surgery (VATS).13
The effects of the nondependent lung ventilation with HFPPV and CPAP on the SVV and fluid responsiveness during OLV has not yet been studied.
Read the detailed description
In all patients, standard monitors, and state and response entropy (SE and RE, respectively) based-depth of anesthesia will be applied. Normothermia will be maintained by using forced-air warming blankets. Anesthetic technique will be standardized in all studied patients. Anesthesiologists who give the anesthetic will be not involved in the collection of outcome data. General anesthesia will be induced with propofol (2-3 mg kg-1) and fentanyl (2-3 µg kg-1) to achieve a SE value less than 50 and the difference between RE and SE less than 10.
Cisatracurium (0.2mg kg-1) will be administered to facilitate the placement of a left-sided double-lumen tube, and the correct position of its tip will be confirmed with a fiberoptic bronchoscope.
Anesthesia will be maintained with 0.7 to 1.5 minimum alveolar concentration of sevoflurane and 0.5 µg kg-1 increments of fentanyl to maintain the SE values less than 50 and the difference between RE and SE less than 10. Suppression of the second twitch in train-of-four stimulation of the ulnar nerve will be maintained with 0.03mg kg-1 increments of cisatracurium.
The radial artery will be catheterized. Cardiac index (CI) and SVV will be measured by using a Vigileo-FloTrac system (v1.14, Edwards Lifescience, Irvine, CA).
Patients' two lungs (TLV) will be mechanically ventilated with a pressure-controlled ventilation mode, a fraction of inspired oxygen (FiO2) of 0.4 in air, TV of 8 mL kg-1 (predicted body weight (PBW)), inspiratory to expiratory (I: E) ratio of 1:2.5 and PEEP of 5 cm H2O, fresh gas flow (FGF) of 1.5-1.7 L min-1, and RR adjusted to achieve a PaCO2 of 35-45 mm Hg.
During OLV,TV, FiO2, I: E ratio, PEEP, FGF, and RR, will be maintained as during TLV and the lumen of the nondependent lung will be left open to air.
After thoracostomy, patients will be randomly allocated to one of two by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code.
The patient's nondependent lung during OLV will be ventilated with a CPAP of 2 cm H2O or HFPPV as randomized.
All patients will receive lactated Ringer's solution at 2mL kg-1 h-1 during surgery. The capability of SVV to predict fluid responsiveness during CPAP or HFPPV will be assessed at 30 min after randomization.
Hemodynamic control will be standardized according to the authors' protocol. If MAP dropped down to 60 mmHg, 250 mL of plasma protein fraction 5% will be administered, and, if this will not enough, repeated doses of intravenous of ephedrine 5 mg or phenylephrine 100 µg, will be administered to maintain urine output to be equal or greater than 0.5 mL kg-1 hour-1. A hemoglobin concentration of 8 g dL-1 or greater will be compensated with red blood cell concentrates.
An independent investigator blinded to the study groups who will not be involved in the patients' management collected the data.
As in previous studies,14-15 the sample size is determined by considering that an area under the ROC curve ≥ 0.8 is clinically reliable to predict fluid responsiveness. To detect a 0.3 difference from the null hypothesis of 0.5, 28 patients will be required in each group with a type-I error of 0.05 and a power of 80% under the ROC curve, assuming equal number of responders and non-responders. To compensate for a dropout rate of 10%, 31 patients will be included in each group.
Normal distributions of data will be assessed using Kolmogorov-Smirnov test. Student's paired t-test or the Wilcoxon signed-rank test will be used to compare hemodynamic variables obtained at the 2 time points (T0, T1) before and after volume expansion. Hemodynamic variables between responders and non-responders within the group at each time point will be compared using Student independent t-test or Mann-Whitney U-test where appropriate. The x2 test will be used when indicated. The Pearson rank method tests linear correlations between SVV before volume loading (T0) and absolute changes in SVV (∆SVV) and percentage change in SVI (∆SVI) after volume. The responders are defined as those patients who demonstrates a ≥ 15% increase in CI after volume expansion between T0 and T1.16 A ROC curve for each variable will be generated and an area under the ROC curve will be calculated. Using this analysis, the optimal threshold value, sensitivity and specificity of SVV during each study intervention could be determined. The ROC curves will be compared using the DeLong test. Data will be expressed as mean ± SD, medians [IQR], or number (%). A value of p< 0.05 is considered to be statistically significant.
- Conditions
- Lung Disease, Undergoing Thoracosocpic Surgery
- Being tested
- High Frequency Positive Pressure Ventilation, Continuous Positive Airway Pressure
- Keywords
- Video-assisted thoracoscopic surgery, one-lung ventilation, continuous positive-airway ventilation, high-frequency positive-pressure ventilation, stroke volume variation, fluid responsiveness
- Medical subject headings
- Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Frequency Positive Pressure VentilationProcedure or surgery
TV 2 mL kg-1 PBW, I:E ratio > 0.3, RR 60 breaths min-1 and a FGF of < 2 L min-1, using a second identical ventilator with low compliant internal circuit
Continuous Positive Airway PressureProcedure or surgery
CPAP of 2 cm H2O
| Study group | Role | What they receive |
|---|---|---|
| High Frequency Positive Pressure Ventilation | Active comparator | Not described Receives: Procedure: High Frequency Positive Pressure Ventilation |
| Continuous Positive Airway Pressure | Placebo comparator | Not described Receives: Procedure: Continuous Positive Airway Pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fluid responsiveness
To explore the ability of SVV to predict fluid responsiveness with ROC plots
Measured: 5 min after volume loading
Secondary outcomes (7)
Heart rate
Measured: 5 min before volume loading, 5 min after volume loading
Stroke volume variation
Measured: 5 min before volume loading, 5 min after volume loading
Mean blood pressure
Measured: 5 min before volume loading, 5 min after volume loading
Cardiac index
Measured: 5 min before volume loading, 5 min after volume loading
Stroke Volume Index
Measured: 5 min before volume loading, 5 min after volume loading
Airway pressures
Measured: 5 min before volume loading, 5 min after volume loading
Lung Compliance
Measured: 5 min before volume loading, 5 min after volume loading
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2014 (estimated)
- Study startJan 2019 (estimated)
- Primary completionApr 2020 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung DiseaseStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imam Abdulrahman Bin Faisal University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Abdulmohsen A Al Ghamdi, MD, Study chair, Chairman of Anesthesiology DeptMohamed R El Tahan, MD, Principal investigator, Imam Abdulrahman Bin Faisal University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02191410
- Sponsor's protocol ID
- N2014045
- Status last verified
- May 2018
- First submitted
- 12 Jul 2014
- Last updated
- 24 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study of the Non-dependent Continuous Positive Airway Pressure and High-frequency Positive-pressure Ventilation on Fluid Responsiveness During One-lung Ventilation for Thoracoscopic Surgery
- ClinicalTrials.gov ID
- NCT02191410
- Acronym / sponsor ID
- N2014045
- Conditions
- Lung Disease, Undergoing Thoracosocpic Surgery
- Keywords
- Video-assisted thoracoscopic surgery, one-lung ventilation, continuous positive-airway ventilation, high-frequency positive-pressure ventilation, stroke volume variation, fluid responsiveness
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Imam Abdulrahman Bin Faisal UniversityUniversity, hospital or other
- Study start
- Jan 2019 (estimated)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 16 Jul 2014 (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.
The stroke volume variation (SVV), measured using the Vigileo-FloTrac system (Edwards Lifescience, Irvine, CA), has been shown to able to predict fluid responsiveness during one-lung ventilation (OLV) in patients undergoing pulmonary lobectomy (sensitivity: 82.4%, specificity: 92.3%).1 Many parameters such as tidal volume (TV),1-2 positive end-expiratory pressure (PEEP),3 respiratory rate (RR), 4 chest and lung compliance,5 heart rate and rhythm, and ventricular function and afterload,6-7 all have been documented to have effects on the SVV.
SVV is calculated as the variation of beat-to-beat SV from the mean value during the most recent 20 seconds of data: SVV = (SVmax - SVmin)/SVmean, where SVmax, SVmin, and SVmean are, respectively, the maximum, minimum, and mean SV determined by the system.
SVV may not be sufficiently sensitive to predict fluid responsiveness in patients with right ventricular (RV) dysfunction due to concomitant increases in RV afterload, that lead to a decrease in preload variation and subsequent inaccuracy in SVV measurements.8
OLV may increase airway pressure, resulting in increases in the RV afterload, end-diastolic volume, and stroke work index, thus impeding RV function.9-11The increases in the right ventricular afterload may exaggerate the cyclic variation in stroke volume.12
In the authors' previous study,9 they found that the high-frequency positive-pressure ventilation (HFPPV) was superior to continuous positive-airway pressure (CPAP) for OLV, resulting in significantly higher RV ejection fraction, lower RV afterload and higher arterial oxygenation, whereas the former limiting the adequate operative field visualization during video-assisted thoracoscopic surgery (VATS).13
The effects of the nondependent lung ventilation with HFPPV and CPAP on the SVV and fluid responsiveness during OLV has not yet been studied.
Detailed description
In all patients, standard monitors, and state and response entropy (SE and RE, respectively) based-depth of anesthesia will be applied. Normothermia will be maintained by using forced-air warming blankets. Anesthetic technique will be standardized in all studied patients. Anesthesiologists who give the anesthetic will be not involved in the collection of outcome data. General anesthesia will be induced with propofol (2-3 mg kg-1) and fentanyl (2-3 µg kg-1) to achieve a SE value less than 50 and the difference between RE and SE less than 10.
Cisatracurium (0.2mg kg-1) will be administered to facilitate the placement of a left-sided double-lumen tube, and the correct position of its tip will be confirmed with a fiberoptic bronchoscope.
Anesthesia will be maintained with 0.7 to 1.5 minimum alveolar concentration of sevoflurane and 0.5 µg kg-1 increments of fentanyl to maintain the SE values less than 50 and the difference between RE and SE less than 10. Suppression of the second twitch in train-of-four stimulation of the ulnar nerve will be maintained with 0.03mg kg-1 increments of cisatracurium.
The radial artery will be catheterized. Cardiac index (CI) and SVV will be measured by using a Vigileo-FloTrac system (v1.14, Edwards Lifescience, Irvine, CA).
Patients' two lungs (TLV) will be mechanically ventilated with a pressure-controlled ventilation mode, a fraction of inspired oxygen (FiO2) of 0.4 in air, TV of 8 mL kg-1 (predicted body weight (PBW)), inspiratory to expiratory (I: E) ratio of 1:2.5 and PEEP of 5 cm H2O, fresh gas flow (FGF) of 1.5-1.7 L min-1, and RR adjusted to achieve a PaCO2 of 35-45 mm Hg.
During OLV,TV, FiO2, I: E ratio, PEEP, FGF, and RR, will be maintained as during TLV and the lumen of the nondependent lung will be left open to air.
After thoracostomy, patients will be randomly allocated to one of two by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code.
The patient's nondependent lung during OLV will be ventilated with a CPAP of 2 cm H2O or HFPPV as randomized.
All patients will receive lactated Ringer's solution at 2mL kg-1 h-1 during surgery. The capability of SVV to predict fluid responsiveness during CPAP or HFPPV will be assessed at 30 min after randomization.
Hemodynamic control will be standardized according to the authors' protocol. If MAP dropped down to 60 mmHg, 250 mL of plasma protein fraction 5% will be administered, and, if this will not enough, repeated doses of intravenous of ephedrine 5 mg or phenylephrine 100 µg, will be administered to maintain urine output to be equal or greater than 0.5 mL kg-1 hour-1. A hemoglobin concentration of 8 g dL-1 or greater will be compensated with red blood cell concentrates.
An independent investigator blinded to the study groups who will not be involved in the patients' management collected the data.
As in previous studies,14-15 the sample size is determined by considering that an area under the ROC curve ≥ 0.8 is clinically reliable to predict fluid responsiveness. To detect a 0.3 difference from the null hypothesis of 0.5, 28 patients will be required in each group with a type-I error of 0.05 and a power of 80% under the ROC curve, assuming equal number of responders and non-responders. To compensate for a dropout rate of 10%, 31 patients will be included in each group.
Normal distributions of data will be assessed using Kolmogorov-Smirnov test. Student's paired t-test or the Wilcoxon signed-rank test will be used to compare hemodynamic variables obtained at the 2 time points (T0, T1) before and after volume expansion. Hemodynamic variables between responders and non-responders within the group at each time point will be compared using Student independent t-test or Mann-Whitney U-test where appropriate. The x2 test will be used when indicated. The Pearson rank method tests linear correlations between SVV before volume loading (T0) and absolute changes in SVV (∆SVV) and percentage change in SVI (∆SVI) after volume. The responders are defined as those patients who demonstrates a ≥ 15% increase in CI after volume expansion between T0 and T1.16 A ROC curve for each variable will be generated and an area under the ROC curve will be calculated. Using this analysis, the optimal threshold value, sensitivity and specificity of SVV during each study intervention could be determined. The ROC curves will be compared using the DeLong test. Data will be expressed as mean ± SD, medians [IQR], or number (%). A value of p< 0.05 is considered to be statistically significant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Frequency Positive Pressure Ventilation | Active comparator | Procedure: High Frequency Positive Pressure Ventilation |
| Continuous Positive Airway Pressure | Placebo comparator | Procedure: Continuous Positive Airway Pressure |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- American Society of Anesthesiologists physical class of II to III
- Duration of OLV is expected to exceed 1.5 hours
Key exclusion criteria (14 listed)
- New York Heart Association class > II
- Right ventricular dysfunction
- Pulmonary hypertension
- valvular heart disease
- intracardiac shunts
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 Positive Pressure VentilationTV 2 mL kg-1 PBW, I:E ratio > 0.3, RR 60 breaths min-1 and a FGF of < 2 L min-1, using a second identical ventilator with low compliant internal circuit | Procedure or surgery | High Frequency Positive Pressure Ventilation |
| Continuous Positive Airway PressureCPAP of 2 cm H2O | Procedure or surgery | Continuous Positive Airway Pressure |
Primary outcome
Fluid responsiveness
Time frame: 5 min after volume loading
To explore the ability of SVV to predict fluid responsiveness with ROC plots
7 secondary outcomes
Heart rate
Time frame: 5 min before volume loading, 5 min after volume loading
Stroke volume variation
Time frame: 5 min before volume loading, 5 min after volume loading
Mean blood pressure
Time frame: 5 min before volume loading, 5 min after volume loading
Cardiac index
Time frame: 5 min before volume loading, 5 min after volume loading
Stroke Volume Index
Time frame: 5 min before volume loading, 5 min after volume loading
Airway pressures
Time frame: 5 min before volume loading, 5 min after volume loading
Lung Compliance
Time frame: 5 min before volume loading, 5 min after volume loading
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
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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.
Abdulmohsen A Al Ghamdi, MD study chair
Chairman of Anesthesiology Dept
Mohamed R El Tahan, MD principal investigator
Imam Abdulrahman Bin Faisal University
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 Positive Pressure Ventilation and Continuous Positive Airway Pressure in people with Lung Disease and Undergoing Thoracosocpic Surgery, run by Imam Abdulrahman Bin Faisal University at 1 site in Saudi Arabia.
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 2 inclusion and 14 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 24 May 2018. 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 Saudi Arabia. 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. Some participants in this study may receive a placebo. 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 Mohamed R El Tahan, MD (+966 13 865 1193, mohamedrefaateltahan@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fluid responsiveness (time frame: 5 min after volume loading). 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 24 May 2018.