HypoxiaPhase 3NCT04807413
Nitric Oxide During Cardiopulmonary Bypass in Adult Surgery
A Phase 3 study testing Nitric Oxide in people with Hypoxia, run by Rabin Medical Center at 1 site in Israel.
Trial summary
Inhaled nitric oxide is a widely accepted standard of care for pulmonary hypertension, and has been studied in the context of cardiac surgery. CPB during cardiac surgery induces systemic inflammatory response and ischemic-reperfusion injury of many organs. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Hypoxia
- What is being tested?
- Nitric Oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteIsrael
- Study dates
- 14 Aug 2021to May 2023
- 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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing elective CABG surgeries with CPB at Rabin Medical Center Beilinson hospital.
- Patients undergoing valve replacement/repair surgeries with CPB at Rabin Medical Center Beilinson hospital.
Who cannot join
- Patients requiring ECMO use preoperatively.
- Patients requiring IABP use preoperatively.
- Patients experiencing preoperative shock (defined as the need for ionotropic and/or vasopressor support).
- Patients after solid organ transplant surgery.
- Patients with LVAD.
- Patients with ESRD requiring dialysis preoperatively.
Show all 9Show fewer
- Patients with a language barrier.
- Patients unable to give informed consent.
- Patients with heparin induced thrombocytopenia.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Rabin Medical Center/Beilinson Campus
Petah Tikva, 49100
Atara Davis
Rosanaa Arnavitsky
About this study
Official title: Nitric Oxide During Cardiopulmonary Bypass in Adult Surgery: A Randomized Double Blinded Trial
Inhaled nitric oxide is a widely accepted standard of care for pulmonary hypertension, and has been studied in the context of cardiac surgery. CPB during cardiac surgery induces systemic inflammatory response and ischemic-reperfusion injury of many organs. Nitric oxide added to the bypass circuit may have anti-inflammatory effect and has shown the potential to ameliorate organs' injury .
There is evidence that the delivery of nitric oxide to the oxygenator gas flow during pediatric CPB is accompanied by a reduction in myocardial injury markers' levels in the postoperative period. In adults, NO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with a lower level of inotropic support and cardio-specific blood markers .
To our knowledge, this is the first trial to assess whether artificial nitric oxide supplementation to the CPB-system reduces the incidence of hypoxemia after cardiac surgery.
Read the detailed description
This prospective, single center, double blinded, interventional trial will be conducted at Rabin Medical Center Beilinson Hospital. Adult patients undergoing CABG and valve replacement/ repair surgeries will be eligible to participate.
All The participant will sign an informed consent prior to any procedures being done specifically for the purpose of the study, in the departmental ward on the day of surgery when they are not under the influence of sedatives and are not in pain. The study design and patient requirements will all be explained to the patient by the study investigator throughout the consent process. Participants will have the opportunity to carefully review the written consent form and ask questions prior to signing. All consent forms will be IRB-approved. Each participant will receive a signed copy of the informed consent document for their record.
Treatment allocation will be performed by an independent investigator who will not be directly involved in the participants' treatment.
All other study investigators will be blinded to a group assignment. All study participants will be blinded to a treatment arm allocation. Upon consent, all study participants will be randomized in a 1:1 ratio to one of the two study arms.
Nitric oxide balloon will be connected to the CPB machine. Study Arm: The balloon will be opened to deliver nitric oxide at 40 ppm. Control Arm: The balloon will be closed and no nitric oxide will be delivered. Following randomization, all study participants will undergo the surgery according to standard clinical practice. In the surgery room all study participants will be connected to a standard anesthesia monitor and will be monitored according to standard clinical practice, which will include monitoring according to ASA standards, insertion of an arterial line and a CVP catheter.
Participation in the study will not affect the anesthetic, surgical and cardiopulmonary bypass management in any way. The anesthetic protocol administered to the study participant is at the attending anesthesiologists' discretion.
In addition to treatment arm allocation, all study participants will be monitored during surgery and followed-up throughout their duration of stay in the ICU and at the department ward.
Throughout the follow-up, study participants' blood tests and vital signs, as routinely monitored, will be collected and documented.
- Conditions
- Hypoxia
- Being tested
- Nitric Oxide, standard of care treatment
- Medical subject headings
- Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
The balloon will be opened to deliver nitric oxide at 40 ppm through the cardiopulmonary bypass machine
standard of care treatmentOther
standard of care treatment
| Study group | Role | What they receive |
|---|---|---|
| Study Arm: The balloon will be opened to deliver nitric oxide at 40 ppm. | Experimental | Nitric oxide balloon will be connected to the CPB machine. Participants randomized to this group will receive 40 ppm nitric oxide through the pump. Receives: Drug: Nitric Oxide |
| Control Arm: The balloon will be closed and no nitric oxide will be delivered. | Active comparator | Participants in this group will receive standard of care treatment. Participation in the trial will not affect surgery management in any way. Receives: Other: standard of care treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of postoperative hypoxemia
Measured: Within 24 hours postoperatively
Secondary outcomes (3)
Incidence of Low cardiac output syndrome
Measured: Within 72 postoperatively
Use of drugs for hemodynamic support such as phenylephrine, noradrenaline
Measured: Within 72 postoperatively
Incidence of Acute Kidney Injury
Measured: Within 72 postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start14 Aug 2021
- Primary completionApr 2023 (estimated)
- Study completionMay 2023 (estimated)
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 HypoxiaStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leonid Eidelman, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807413
- Sponsor's protocol ID
- 0056-21
- Status last verified
- Mar 2021
- First submitted
- 18 Mar 2021
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Azem K, Novakovsky D, Krasulya B, Fein S, Iluz-Freundlich D, Uhanova J, Kornilov E, Eidelman LA, Kaptzon S, Gorfil D, Aravot D, Barac Y, Aranbitski R. Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial. Eur J Anaesthesiol. 2024 Sep 1;41(9):677-686. doi: 10.1097/EJA.0000000000002022. Epub 2024 May 28.
PubMed 39037709
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitric Oxide During Cardiopulmonary Bypass in Adult Surgery: A Randomized Double Blinded Trial
- ClinicalTrials.gov ID
- NCT04807413
- Acronym / sponsor ID
- 0056-21
- Conditions
- Hypoxia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- 14 Aug 2021 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 19 Mar 2021 (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.
Inhaled nitric oxide is a widely accepted standard of care for pulmonary hypertension, and has been studied in the context of cardiac surgery. CPB during cardiac surgery induces systemic inflammatory response and ischemic-reperfusion injury of many organs. Nitric oxide added to the bypass circuit may have anti-inflammatory effect and has shown the potential to ameliorate organs' injury .
There is evidence that the delivery of nitric oxide to the oxygenator gas flow during pediatric CPB is accompanied by a reduction in myocardial injury markers' levels in the postoperative period. In adults, NO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with a lower level of inotropic support and cardio-specific blood markers .
To our knowledge, this is the first trial to assess whether artificial nitric oxide supplementation to the CPB-system reduces the incidence of hypoxemia after cardiac surgery.
Detailed description
This prospective, single center, double blinded, interventional trial will be conducted at Rabin Medical Center Beilinson Hospital. Adult patients undergoing CABG and valve replacement/ repair surgeries will be eligible to participate.
All The participant will sign an informed consent prior to any procedures being done specifically for the purpose of the study, in the departmental ward on the day of surgery when they are not under the influence of sedatives and are not in pain. The study design and patient requirements will all be explained to the patient by the study investigator throughout the consent process. Participants will have the opportunity to carefully review the written consent form and ask questions prior to signing. All consent forms will be IRB-approved. Each participant will receive a signed copy of the informed consent document for their record.
Treatment allocation will be performed by an independent investigator who will not be directly involved in the participants' treatment.
All other study investigators will be blinded to a group assignment. All study participants will be blinded to a treatment arm allocation. Upon consent, all study participants will be randomized in a 1:1 ratio to one of the two study arms.
Nitric oxide balloon will be connected to the CPB machine. Study Arm: The balloon will be opened to deliver nitric oxide at 40 ppm. Control Arm: The balloon will be closed and no nitric oxide will be delivered. Following randomization, all study participants will undergo the surgery according to standard clinical practice. In the surgery room all study participants will be connected to a standard anesthesia monitor and will be monitored according to standard clinical practice, which will include monitoring according to ASA standards, insertion of an arterial line and a CVP catheter.
Participation in the study will not affect the anesthetic, surgical and cardiopulmonary bypass management in any way. The anesthetic protocol administered to the study participant is at the attending anesthesiologists' discretion.
In addition to treatment arm allocation, all study participants will be monitored during surgery and followed-up throughout their duration of stay in the ICU and at the department ward.
Throughout the follow-up, study participants' blood tests and vital signs, as routinely monitored, will be collected and documented.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Arm: The balloon will be opened to deliver nitric oxide at 40 ppm. | Experimental | Drug: Nitric OxideNitric oxide balloon will be connected to the CPB machine. Participants randomized to this group will receive 40 ppm nitric oxide through the pump. |
| Control Arm: The balloon will be closed and no nitric oxide will be delivered. | Active comparator | Other: standard of care treatmentParticipants in this group will receive standard of care treatment. Participation in the trial will not affect surgery management in any way. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients undergoing elective CABG surgeries with CPB at Rabin Medical Center Beilinson hospital.
- Patients undergoing valve replacement/repair surgeries with CPB at Rabin Medical Center Beilinson hospital.
Key exclusion criteria (9 listed)
- Patients requiring ECMO use preoperatively.
- Patients requiring IABP use preoperatively.
- Patients experiencing preoperative shock (defined as the need for ionotropic and/or vasopressor support).
- Patients after solid organ transplant surgery.
- Patients with LVAD.
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 OxideThe balloon will be opened to deliver nitric oxide at 40 ppm through the cardiopulmonary bypass machine | Drug | Study Arm: The balloon will be opened to deliver nitric oxide at 40 ppm. |
| standard of care treatmentstandard of care treatment | Other | Control Arm: The balloon will be closed and no nitric oxide will be delivered. |
Primary outcome
Incidence of postoperative hypoxemia
Time frame: Within 24 hours postoperatively
3 secondary outcomes
Incidence of Low cardiac output syndrome
Time frame: Within 72 postoperatively
Use of drugs for hemodynamic support such as phenylephrine, noradrenaline
Time frame: Within 72 postoperatively
Incidence of Acute Kidney Injury
Time frame: Within 72 postoperatively
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Derived from this study: PubMed 39037709Azem K, Novakovsky D, Krasulya B, Fein S, Iluz-Freundlich D, Uhanova J, Kornilov E, Eidelman LA, Kaptzon S, Gorfil D, Aravot D, Barac Y, Aranbitski R. Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial. Eur J Anaesthesiol. 2024 Sep 1;41(9):677-686. doi: 10.1097/EJA.0000000000002022. Epub 2024 May 28.
- Individual participant dataSharing planned: Undecided
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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.
Leonid Eidelman principal investigator
Rabin Medical Center
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 Nitric Oxide in people with Hypoxia, run by Rabin Medical Center at 1 site in Israel.
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 9 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 8 Oct 2021. 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 Israel. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Leonid Eidelman, MD (97239376850, leidelman@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of postoperative hypoxemia (time frame: Within 24 hours postoperatively). 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 NCT04807413, 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 8 Oct 2021.