AnesthesiaPhase 3NCT02523859
Study of the Efficacy and Safety of Remimazolam in General Anesthesia in Adults Undergoing Cardiac Surgery
A Phase 3 study testing Propofol and Remimazolam in people with Anesthesia, run by Paion UK Ltd. at 1 site in Germany.
Trial summary
This study investigates the use of remimazolam as a sedative/hypnotic in general anesthesia. Remimazolam or propofol will be administered together with fentanyl/sufentanil/remifentanil as opioid analgesics and a neuromuscular blocker. In total, 530 patients will be randomized. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anesthesia
- What is being tested?
- Propofol and Remimazolam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2015to Mar 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled for major non-emergency cardiac surgery, i.e. surgery assumed to require more than 2 hours of maintenance of general anesthesia and to require the use of extracorporeal circulation, including coronary bypass(es), valve replacement(s), and associated procedures and on-pump minimal invasive surgery
- Scheduled to receive mechanical ventilation via tracheal intubation (oropharyngeal or nasotracheal)
- Age at least 18 years
- Body mass index 18 to ≤40 kg/m2
- Willingness and ability to give informed consent, to understand, participate and comply with all study requirements
- For women of childbearing potential: negative pregnancy test (serum or urine strip) as well as using a highly effective method of birth control. Such methods include:
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- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, with the following routes of administration: oral, intravaginal, transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation, with the following routes of administration: oral, injectable, implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Sexual abstinence A woman was considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods included hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
Who cannot join
- Re-do cardiac surgery
- Surgical procedures that comprised the use of drugs and/or devices that were not approved for marketing
- Severe tricuspidal insufficiency (III grade)
- Planned cooling of the patient's body below 32ºC
- History of or planned stop of circulation, e.g. due to repair of type A dissection of aorta or removal of thrombi from pulmonary artery
- Planned to receive epidural/spinal anesthesia together with general anesthesia
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- Evidence of uncontrolled hepatic, central nervous system, respiratory, or metabolic dysfunction, or other clinically significant findings at screening that, in the investigator's or medical monitor's opinion, excluded patients from the study
- Poorly controlled hypertension (e.g. systolic blood pressure ≥160 mmHg under antihypertensive medication at screening)
- Patients with severe renal insufficiency or end-stage renal disease (creatinine clearance below 30 mL/min or estimated glomerular filtration rate below 30 mL/min/1.73 m2). Measuring only one of both parameters was sufficient to assess the eligibility of a patient.
- Patients with clinically uncontrolled coagulation abnormalities, or with coagulation abnormalities not under adequate treatment
- Patients scheduled for heart or lung transplantation
- Patients with infectious cardiac disorders (e.g. endocarditis, myocarditis)
- Patients with sepsis
- Emergency surgery, status of shock or coma
- Patients with an ejection fraction from the left ventricle of less than 20%
- Patients with acute right heart failure
- Pre-operative use of phosphodiesterase 3 inhibitors
- Patients with a history of resuscitation
- Known resistance to benzodiazepines or history of paradoxical effects after administration of benzodiazepines
- History of hypersensitivity to benzodiazepines, propofol, remifentanil hydrochloride, neuromuscular blockers, flumazenil or other anesthetic agents
- Use of benzodiazepines within 5 times their half-life or 5 times the half-life of their active metabolites. Exception: Pre-medication with a benzodiazepine according to local standards was allowed.
- Epilepsy
- Myasthenia gravis or myasthenic syndrome
- History of any severe allergy defined as urticaria, angioedema or anaphylaxis
- Dependence from drugs or history of drug abuse
- Dependence from alcohol or history of alcohol abuse within the last 5 years
- Acute alcoholic intoxication or ethanol intake within 48 hours prior to surgery
- Acute narrow-angle glaucoma
- Female patients of childbearing potential without acceptable method of birth control (for definitions: see inclusion criterion 6).
- Pregnant or breast-feeding female patients
- Patients in receipt of any investigational drug within 30 days or less than 7 half-lives (whichever was longer) before the start of the study, or scheduled to receive one during the study period.
- Administration of remimazolam in the past
- Patients unable to communicate with the investigator as required for the study
- Other reasons that, according to the investigator, excluded the patient from the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Single-blind, Propofol-controlled Phase III Study Evaluating the Efficacy and Safety of Remimazolam in GA in Adult Patients Undergoing Cardiac Surgery, Including Follow-up Sedation in the Post-anesthesia Care Unit/ICU
This study investigates the use of remimazolam as a sedative/hypnotic in general anesthesia. Remimazolam or propofol will be administered together with fentanyl/sufentanil/remifentanil as opioid analgesics and a neuromuscular blocker.
In total, 530 patients will be randomized. This group of 530 patients will be split randomly into 2 groups as follows:
Read more
- 106 patients will be randomized to induction with propofol plus fentanyl or sufentanil or remifentanil and a neuromuscular blocker. Throughout maintenance, the patients will receive propofol and remifentanil until weaning from the mechanical ventilation on the ICU or PACU within 24 hours after induction.
Afterwards, sedation with propofol as study medication has to be ended. If necessary, the sedation is to be continued with the hospital's own supplies (propofol or other sedative).
- 424 patients will be randomized to induction with remimazolam 6.0 mg/kg/hr together with fentanyl or sufentanil or remifentanil and a neuromuscular blocker. Throughout maintenance, the patients will receive remimazolam and remifentanil until weaning from the mechanical ventilation on the ICU or PACU within 24 hours after induction.
The primary endpoint is successful sedation is defined as a Narcotrend index of 60 or less during at least 85% of the maintenance time and no rescue sedative medication administered. The maintenance starts at arrival at the operation theater and ends with the completion of the last skin suture.
- Conditions
- Anesthesia
- Being tested
- Propofol, Remimazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Also called Diprivan
Hypnotic drug used for anesthesia
RemimazolamDrug
Also called CNS7056
Benzodiazepine being developed for sedation and anesthesia.
| Study group | Role | What they receive |
|---|---|---|
| Propofol | Active comparator | Propofol for induction will be given as a bolus administered manually at 2.0-2.5 mg/kg slowly over approximately 1 minute. Immediately after the propofol bolus for induction has been given, propofol maintenance will be started at a dose of 3.0-9.0 mg/kg/hr and adjusted as needed. Receives: Drug: Propofol |
| Remimazolam | Experimental | Remimazolam for induction will be given at 6.0 mg/kg/hr, which can be increased to 12.0 mg/kg/hr for one minute if loss of consciousness is not reached after 3 minutes. Immediately after the remimazolam dose for induction has been given, remimazolam maintenance will be given at 1.0 mg/kg/hr and adjusted by down-titration or up-titration to a maximum of 3.0 mg/kg/hr. Receives: Drug: Remimazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success of Procedure
A narcotrend index of 60 or less during at least 85% of the maintenance time and no rescue sedative medication administered.
Measured: During maintenance phase of operation - between arrival at operation theatre and completion of last skin suture (estimated up to 24 hours).
Secondary outcomes (1)
Hemodynamic stability
Expressed as the amount of norepinephrine used.
Measured: From the start of study medication until completion of the last skin suture (estimated up to 24 hours).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2015 (estimated)
- Study startJul 2015
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnesthesiaStudies 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
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paion UK Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Stefan Probst, MD, Principal investigator, Herzzentrum Leipzig GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02523859
- Sponsor's protocol ID
- CNS7056-011
- Status last verified
- Aug 2023
- First submitted
- 11 Aug 2015
- Last updated
- 30 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Single-blind, Propofol-controlled Phase III Study Evaluating the Efficacy and Safety of Remimazolam in GA in Adult Patients Undergoing Cardiac Surgery, Including Follow-up Sedation in the Post-anesthesia Care Unit/ICU
- ClinicalTrials.gov ID
- NCT02523859
- Acronym / sponsor ID
- CNS7056-011
- Conditions
- Anesthesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- Jul 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 14 Aug 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.
This study investigates the use of remimazolam as a sedative/hypnotic in general anesthesia. Remimazolam or propofol will be administered together with fentanyl/sufentanil/remifentanil as opioid analgesics and a neuromuscular blocker.
In total, 530 patients will be randomized. This group of 530 patients will be split randomly into 2 groups as follows:
- 106 patients will be randomized to induction with propofol plus fentanyl or sufentanil or remifentanil and a neuromuscular blocker. Throughout maintenance, the patients will receive propofol and remifentanil until weaning from the mechanical ventilation on the ICU or PACU within 24 hours after induction.
Afterwards, sedation with propofol as study medication has to be ended. If necessary, the sedation is to be continued with the hospital's own supplies (propofol or other sedative).
- 424 patients will be randomized to induction with remimazolam 6.0 mg/kg/hr together with fentanyl or sufentanil or remifentanil and a neuromuscular blocker. Throughout maintenance, the patients will receive remimazolam and remifentanil until weaning from the mechanical ventilation on the ICU or PACU within 24 hours after induction.
The primary endpoint is successful sedation is defined as a Narcotrend index of 60 or less during at least 85% of the maintenance time and no rescue sedative medication administered. The maintenance starts at arrival at the operation theater and ends with the completion of the last skin suture.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propofol | Active comparator | Drug: PropofolPropofol for induction will be given as a bolus administered manually at 2.0-2.5 mg/kg slowly over approximately 1 minute. Immediately after the propofol bolus for induction has been given, propofol maintenance will be started at a dose of 3.0-9.0 mg/kg/hr and adjusted as needed. |
| Remimazolam | Experimental | Drug: RemimazolamRemimazolam for induction will be given at 6.0 mg/kg/hr, which can be increased to 12.0 mg/kg/hr for one minute if loss of consciousness is not reached after 3 minutes. Immediately after the remimazolam dose for induction has been given, remimazolam maintenance will be given at 1.0 mg/kg/hr and adjusted by down-titration or up-titration to a maximum of 3.0 mg/kg/hr. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Scheduled for major non-emergency cardiac surgery, i.e. surgery assumed to require more than 2 hours of maintenance of general anesthesia and to require the use of extracorporeal circulation, including coronary bypass(es), valve replacement(s), and associated procedures and on-pump minimal invasive surgery
- Scheduled to receive mechanical ventilation via tracheal intubation (oropharyngeal or nasotracheal)
- Age at least 18 years
- Body mass index 18 to ≤40 kg/m2
- Willingness and ability to give informed consent, to understand, participate and comply with all study requirements
Key exclusion criteria (34 listed)
- Re-do cardiac surgery
- Surgical procedures that comprised the use of drugs and/or devices that were not approved for marketing
- Severe tricuspidal insufficiency (III grade)
- Planned cooling of the patient's body below 32ºC
- History of or planned stop of circulation, e.g. due to repair of type A dissection of aorta or removal of thrombi from pulmonary artery
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 |
|---|---|---|
| PropofolAlso: DiprivanHypnotic drug used for anesthesia | Drug | Propofol |
| RemimazolamAlso: CNS7056Benzodiazepine being developed for sedation and anesthesia. | Drug | Remimazolam |
Primary outcome
Success of Procedure
Time frame: During maintenance phase of operation - between arrival at operation theatre and completion of last skin suture (estimated up to 24 hours).
A narcotrend index of 60 or less during at least 85% of the maintenance time and no rescue sedative medication administered.
1 secondary outcome
Hemodynamic stability
Time frame: From the start of study medication until completion of the last skin suture (estimated up to 24 hours).
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
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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.
Stefan Probst, MD principal investigator
Herzzentrum Leipzig GmbH
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 Propofol and Remimazolam in people with Anesthesia, run by Paion UK Ltd. at 1 site in Germany.
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 12 inclusion and 34 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: stopped early, as of the sponsor's last update on 30 Aug 2023. 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 Germany. 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 was stopped early (reason given: Poor recruitment). Results are not available in the source record.
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?
Success of Procedure (time frame: During maintenance phase of operation - between arrival at operation theatre and completion of last skin suture (estimated up to 24 hours).). 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 30 Aug 2023.