Pulmonary HypertensionPhase 2NOCaPHNCT02345616
Role of the Nitric Oxide (NO) in Pre-oxygenation Before Anesthetic Induction in Patients With a Pulmonary Hypertension in Cardiac Surgery. Pilot Study of Feasibility
A Phase 2 study testing Nitric oxide in people with Pulmonary Hypertension, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
The pulmonary hypertension (HTP) due to a left heart disease or a hypoxemiant lung disease is frequent in cardiac surgery. The HTP represents an independent risk factor of morbidity and mortality in cardiac surgery, entering to the criteria of Euroscore evaluation (European System for Cardiac Operative Risk… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Nitric oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2015to Dec 2019
- Phase
- Phase 2
- 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
- Age > 18 years old
- Open-heart cardiac surgery
- HTP Pulmonary hypertension (class 2 or 3) with PAPs (Systolic pulmonary artery pressure) > 40 mmHg diagnosed by preoperative righ cardiac catheterization or by transthoracic echocardiography.
- Patient have signed their consent according to the modalities described by the Code of Public health system.
- Patients affiliated to a national insurance (social security) system.
Who cannot join
- Heart transplant
- HTP of type 1, 4, 5 according to the classification of Dana Point(2008)
- Deficit in methemoglobin reductase
- Protocole refuse from patient
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand, 63003
Patrick LACARIN, 04 73 75 11 95, placarin@chu-clermontferrand.fr
Henri BOBY
About this study
The pulmonary hypertension (HTP) due to a left heart disease or a hypoxemiant lung disease is frequent in cardiac surgery. The HTP represents an independent risk factor of morbidity and mortality in cardiac surgery, entering to the criteria of Euroscore evaluation (European System for Cardiac Operative Risk Evaluation).
An acute perioperative hemodynamic decompensation of these patients is frequent. Perioperative hemodynamic modifications, hypoxemia, hypercapnia, sympathetic stimulation, increase pulmonary vascular resistances (RVP) and might provoke right ventricular failure.
Read more
The anesthetic induction and the beginning of mechanical ventilation are the most sensible times due to the risk of hemodynamic decompensation. The suppression of the sympathetic tonus which is consequence of the anesthetic induction, decrease the systemic vascular resistances and lead to decrease of blood pressure. In return, the anesthetic induction is associated with an increase of pulmonary vascular resistances, resulting in increase of the postcharge and the work of the right ventricle (VD). These systemic and pulmonary hemodynamic modifications can lead to equalization, or even an inversion of the systemic and pulmonary pressures. As consequence, a hemodynamic collapse or even a heart arrest can arise.
The patients suffering from HTP are hypoxemic. They have very limited oxygen reserves due to decrease of the functional residual capacity (CRF). The apnea period, which follows the anesthetic induction, is often associated with a fast desaturation, even if a good pre-oxygenation was performed before. This desaturation causes an increase of the pulmonary vascular resistances with the hemodynamic consequences previously mentioned. A risk of hypoxic heart arrest is also present.
Nitric Oxide (NO) is an endogenous mediator produced from the vascular endothelium. The NO is a powerful vasodilator and is used in intensive care in inhaled way as selective pulmonary vasodilator (iNO). NO decreases the RVP, the shunt effect and improves the oxygenation by optimization of ventilation-perfusion ratio. The short lifetime of iNO (6sec approximately) allows a fast metabolism without inducing any undesirable effects such as the systemic hypotension.
No studies, until now, have investigated the use of iNO in pre-oxygenation before anesthetic induction in cardiac surgery.
We hope to demonstrate that iNO used in oxygenation before anesthetic induction will have a beneficial effect on the respiratory and cardiovascular parameters.
Our objective is to estimate the feasibility and the tolerance of iNO before anesthetic induction of the patients with a moderate or severe HTP programmed for cardiac surgery with extracorporeal circulation. The effect will be estimated in terms of efficiency (hemodynamic and respiratory optimization).
Read the detailed description
Before the anesthetic induction every included patient will follow these protocol:
- Standard monitoring (ECG Electrocardiogram, SpO2 Pulsed oxygen saturation)
- Insertion of radial arterial line and periferic IV line under local anesthesia,
- Insertion of a internal jugular central line and Swan Ganz catheter under local anesthesia
- Preoxygenation in 100% oxygen for 10 min
- Further preoxygenation with a mixture of 100% oxygen associated with the iNO in a dose of 1,2 L / mn.
- Anesthesia induction and initiation of mechanical ventilation.
- Progressive decrease of iNO dose and stop of iNO administration.
- Conditions
- Pulmonary Hypertension
- Being tested
- Nitric oxide
- Keywords
- Cardiac surgery, Pulmonary hypertension, Nitric oxide, Induction anesthesia
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric oxideDrug
| Study group | Role | What they receive |
|---|---|---|
| Nitric oxyde | Experimental | Not described Receives: Drug: Nitric oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary arterial systolic, diastolic and mean pressure
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
Pulmonary arterial mean/arterial mean ratio
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
SpO2 (Pulsed oxygen saturation)
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
FeO2 (Fraction expired oxygen) (data not available just during intubation phase)
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
Cardiac index
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
Systemic vascular resistances
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
SVO2 (Central Venous Saturation)
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
Sat O2 (Blood oxygen saturation)
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
PaO2 (Partial pressure of arterial oxygen)
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
MetHb (methemoglobin)
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
Secondary outcomes (1)
Systolic, diastolic and mean arterial pressure
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Measured: at day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2015 (estimated)
- Study startFeb 2015
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Collaborators
- ARAMU Association
- Responsible party
- Sponsor
- Investigators
- Vedat ELJEZI, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02345616
- Sponsor's protocol ID
- CHU-0221
- Other IDs
- 2014-003338-15, 2014
- Acronym
- NOCaPH
- Status last verified
- Feb 2019
- First submitted
- 20 Jan 2015
- Last updated
- 4 Feb 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the Nitric Oxide (NO) in Pre-oxygenation Before Anesthetic Induction in Patients With a Pulmonary Hypertension in Cardiac Surgery. Pilot Study of Feasibility
- ClinicalTrials.gov ID
- NCT02345616
- Acronym / sponsor ID
- NOCaPH / CHU-0221
- Conditions
- Pulmonary Hypertension
- Keywords
- Cardiac surgery, Pulmonary hypertension, Nitric oxide, Induction anesthesia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Collaborators
- ARAMU Association
- Study start
- Feb 2015
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 26 Jan 2015 (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 pulmonary hypertension (HTP) due to a left heart disease or a hypoxemiant lung disease is frequent in cardiac surgery. The HTP represents an independent risk factor of morbidity and mortality in cardiac surgery, entering to the criteria of Euroscore evaluation (European System for Cardiac Operative Risk Evaluation).
An acute perioperative hemodynamic decompensation of these patients is frequent. Perioperative hemodynamic modifications, hypoxemia, hypercapnia, sympathetic stimulation, increase pulmonary vascular resistances (RVP) and might provoke right ventricular failure.
The anesthetic induction and the beginning of mechanical ventilation are the most sensible times due to the risk of hemodynamic decompensation. The suppression of the sympathetic tonus which is consequence of the anesthetic induction, decrease the systemic vascular resistances and lead to decrease of blood pressure. In return, the anesthetic induction is associated with an increase of pulmonary vascular resistances, resulting in increase of the postcharge and the work of the right ventricle (VD). These systemic and pulmonary hemodynamic modifications can lead to equalization, or even an inversion of the systemic and pulmonary pressures. As consequence, a hemodynamic collapse or even a heart arrest can arise.
The patients suffering from HTP are hypoxemic. They have very limited oxygen reserves due to decrease of the functional residual capacity (CRF). The apnea period, which follows the anesthetic induction, is often associated with a fast desaturation, even if a good pre-oxygenation was performed before. This desaturation causes an increase of the pulmonary vascular resistances with the hemodynamic consequences previously mentioned. A risk of hypoxic heart arrest is also present.
Nitric Oxide (NO) is an endogenous mediator produced from the vascular endothelium. The NO is a powerful vasodilator and is used in intensive care in inhaled way as selective pulmonary vasodilator (iNO). NO decreases the RVP, the shunt effect and improves the oxygenation by optimization of ventilation-perfusion ratio. The short lifetime of iNO (6sec approximately) allows a fast metabolism without inducing any undesirable effects such as the systemic hypotension.
No studies, until now, have investigated the use of iNO in pre-oxygenation before anesthetic induction in cardiac surgery.
We hope to demonstrate that iNO used in oxygenation before anesthetic induction will have a beneficial effect on the respiratory and cardiovascular parameters.
Our objective is to estimate the feasibility and the tolerance of iNO before anesthetic induction of the patients with a moderate or severe HTP programmed for cardiac surgery with extracorporeal circulation. The effect will be estimated in terms of efficiency (hemodynamic and respiratory optimization).
Detailed description
Before the anesthetic induction every included patient will follow these protocol:
- Standard monitoring (ECG Electrocardiogram, SpO2 Pulsed oxygen saturation)
- Insertion of radial arterial line and periferic IV line under local anesthesia,
- Insertion of a internal jugular central line and Swan Ganz catheter under local anesthesia
- Preoxygenation in 100% oxygen for 10 min
- Further preoxygenation with a mixture of 100% oxygen associated with the iNO in a dose of 1,2 L / mn.
- Anesthesia induction and initiation of mechanical ventilation.
- Progressive decrease of iNO dose and stop of iNO administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nitric oxyde | Experimental | Drug: Nitric oxide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years old
- Open-heart cardiac surgery
- HTP Pulmonary hypertension (class 2 or 3) with PAPs (Systolic pulmonary artery pressure) > 40 mmHg diagnosed by preoperative righ cardiac catheterization or by transthoracic echocardiography.
- Patient have signed their consent according to the modalities described by the Code of Public health system.
- Patients affiliated to a national insurance (social security) system.
Key exclusion criteria (4 listed)
- Heart transplant
- HTP of type 1, 4, 5 according to the classification of Dana Point(2008)
- Deficit in methemoglobin reductase
- Protocole refuse from patient
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 |
|---|---|---|
| Nitric oxide | Drug | Nitric oxyde |
Primary outcome
Pulmonary arterial systolic, diastolic and mean pressure
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Pulmonary arterial mean/arterial mean ratio
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
SpO2 (Pulsed oxygen saturation)
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
FeO2 (Fraction expired oxygen) (data not available just during intubation phase)
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Cardiac index
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Systemic vascular resistances
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
SVO2 (Central Venous Saturation)
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
Sat O2 (Blood oxygen saturation)
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
PaO2 (Partial pressure of arterial oxygen)
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
MetHb (methemoglobin)
Time frame: at day 1
These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)
1 secondary outcome
Systolic, diastolic and mean arterial pressure
Time frame: at day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2019.
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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.
Vedat ELJEZI principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric oxide in people with Pulmonary Hypertension, run by University Hospital, Clermont-Ferrand at 1 site in France.
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 4 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 4 Feb 2019. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Patrick LACARIN (04 73 75 11 95, placarin@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulmonary arterial systolic, diastolic and mean pressure (time frame: at day 1). The study lists 10 primary outcomes in all. 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 4 Feb 2019.