Anesthesia, IntravenousPhase 3NCT03661489
Efficacy and Safety of Remimazolam (CNS7056) Compared to Propofol for Intravenous Anesthesia During Elective Surgery
A Phase 3 study testing Remimazolam and Propofol in people with Anesthesia, Intravenous, run by Paion UK Ltd. at 1 site in Germany.
Trial summary
A phase III confirmatory trial evaluating the efficacy and safety of remimazolam (CNS7056) compared to propofol for intravenous anesthesia during elective surgery in ASA Class III/IV patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anesthesia, Intravenous
- What is being tested?
- Remimazolam and Propofol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 469 participants
- Where
- 1 siteGermany
- Study dates
- 24 Jul 2018to 2 Apr 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ASA III/IV patients at least 18 years old, scheduled for an elective surgical procedure of a minimum duration of approximately 90 minutes under general anesthesia (GA) and planned to be extubated immediately post-operatively.
- Total intravenous GA with the requirement for mechanical ventilation via endotracheal tube and necessary invasive blood pressure (BP) monitoring either due to severity of illness, severity of concomitant diseases, type of surgery or decisions of the anesthesia staff.
- Patients scheduled to stay in the hospital long enough after the surgical procedure to perform all trial follow-up procedures (~1 day)
- For female patients of childbearing potential: Negative result of a pregnancy test taken shortly before the start of the administration of the IMP as well as consent to use highly effective birth control from the last menstrual cycle prior to the start of the IMP until the end of the trial follow-up procedures. Highly effective methods of birth control include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal and transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable and implantable
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- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomised partner (provided that the partner is the sole sexual partner of the female patient of childbearing potential and that the vasectomised partner has received medical assessment of the surgical success)
- Sexual abstinence (this method is not acceptable in Switzerland)
- Women who had their last menstruation at least two years ago or who underwent surgical interventions (surgical birth control, bilateral oophorectomy, hysterectomy, etc.) are regarded as having no childbearing potential
Who cannot join
- Patients scheduled for spinal anesthesia, epidural anesthesia (central neuraxial anesthesia) or regional anesthesia. The placement of a peridural catheter with a test dose application of a local anesthetic drug (up to 5 mL) to verify correct positioning to achieve post-operative analgesia and the regional administration of local anesthetic for post-operative analgesia after wound closure is accepted.
- Patients undergoing transplant surgery, cardiac surgery, or intracranial neurosurgery, patients which have to be in prone position for surgery, emergency surgery, or any surgical procedure with the need for or scheduled for post-operative ventilator support.
- Patients undergoing surgical procedures that require keeping the BP at a high level, e.g. surgical procedures in beach chair position
- Patients with severe hypertension, i.e., one baseline result of systolic BP 200 mmHg or more and / or diastolic BP of 120 mmHg or more. Baseline is defined as the time after signature of the informed consent form (ICF) and before arrival in the operating room (OR) suite.
- Patients with total bilirubin of ≥3.0 mg/dL or ≥3 times increase in aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) than the institutional reference range in laboratory tests, or any other laboratory results that make the patient unsuitable for the trial. All laboratory tests relevant for subject's enrolment must be performed within 7 days prior to start of IMP*
- If the screening samples for the central laboratory were taken earlier than within the last 7 days prior to start of IMP, the lab parameters relevant for subject's enrolment are to be determined in a local laboratory within 7 days prior to start of IMP. If results from samples taken within 7 days prior to the start of the IMP/the surgery from a local laboratory are available, these can be used. If no results from the last 7 days prior to the start of the IMP/the surgery are available, samples need to be taken for the purpose of this trial and to be analysed in a local laboratory.
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- Patients with end stage renal disease (ESRD) requiring scheduled dialysis
- Patients with known anaphylactic reactions to benzodiazepines, propofol, opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), dextran, neuromuscular blocking agents, flumazenil, naloxone, or other anesthetic agents, or a medical condition such that these agents are contraindicated (according to local label)
- Presence of acute alcoholic or illicit drug intoxication, shock or coma state
- Known current dependency from central nervous system depressant drugs or alcohol
- Patients with gastroparesis or delayed gastric emptying, gastric reflux or any other increased risk for gastric aspiration
- Patients with an anticipated (small mouth opening, impaired neck movement, goitre, head and neck tumours or any other anatomical reason) or known airway difficulties or with known difficulties in airway maintenance or mask ventilation
- Patients in whom Narcotrend (NCT) may not provide reliable results due to organic defect of the brain or forehead, or any neurologic disease interfering with the EEG monitoring
- Patients on treatment with valproate
- Any pregnant or breast-feeding patient
- Patients who participated in any clinical trial within 30 days or 5 times the half-life of the drug under investigation, whichever is longer, prior to the beginning of administration of the IMP. Exception: Non-interventional trials as defined in the European Clinical Trials Directive 2001/20/EC: A trial where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorisation. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnostic or monitoring procedures shall be applied to the patients and epidemiological methods should be used for the analysis of the collected data.
- Any patient judged to lack the ability to give informed consent or perform the trial assessments (e.g., due to dementia)
- Any patient judged by the Principal Investigator (PI) or Sub-Investigator to be inappropriate for the subject for any other reason
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Confirmatory Efficacy and Safety Trial of Remimazolam (CNS7056) Compared With Propofol for Intravenous Anesthesia During Elective Surgery in ASA Class III/IV Patients
A phase III confirmatory trial evaluating the efficacy and safety of remimazolam (CNS7056) compared to propofol for intravenous anesthesia during elective surgery in ASA Class III/IV patients.
Read the detailed description
This is a Phase III single-blind, randomized, controlled, non-inferiority multi-center trial in American Society of Anesthesiologists (ASA) Class III/IV patients undergoing elective surgery, comparing remimazolam to propofol for induction and maintenance of intravenous anesthesia. In accordance with general anesthetic standard regimen, remimazolam or propofol, will be administered together with remifentanil as analgesic agent, and with a neuromuscular blocker to facilitate intubation and achieve muscle relaxation
- Conditions
- Anesthesia, Intravenous
- Being tested
- Remimazolam, Propofol
- Keywords
- remimazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemimazolamDrug
For induction and maintenance of general anesthesia
PropofolDrug
For induction and maintenance of general anesthesia
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Remimazolam 50 mg | Experimental | For induction of general anesthesia, remimazolam is co-administered with remifentanil for analgesia and with a muscle relaxant as necessary.
For maintenance of general anesthesia remimazolam is titrated to effect. Administration of boluses of remimazolam is allowed. Remifentanil is continued and/or titrated. Boluses of muscle relaxants are given throughout the surgical procedure as needed. Receives: Drug: Remimazolam |
| Intravenous Propofol 2% | Active comparator | For induction of general anesthesia, propofol is co-administered with remifentanil for analgesia and with a muscle relaxant as necessary.
For maintenance of general anesthesia propofol is titrated to effect. Administration of boluses of propofol is allowed. Remifentanil is continued and/or titrated. Boluses of muscle relaxants are given throughout the surgical procedure as needed. Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage (%) of time of Narcotrend Index (NCI) values ≤ 60 during maintenance phase of general anesthesia (defined as time between the first skin incision and the completion of the last skin suture)
The primary efficacy endpoint (PEP) is the anesthetic effect of remimazolam and propofol assessed as percent (%) of time of NCI ≤60 during the maintenance phase of general anesthesia
Measured: maintenance phase of general anesthesia (time between the first skin incision and the completion of the last skin suture)
Secondary outcomes (1)
Number of events of critical decrease(s) in mean arterial blood pressure (MAP)
For this endpoint, each event from the following categories will be counted and summed up per patient:
- Incidence of MAP dropping below 65 mmHg for at least 1 minute duration
- Incidence of a MAP decrease of more than 20% below the calculated (mean) baseline MAP value for at least 1 minute duration
- Incidence of a MAP decrease of more than 30% below the calculated (mean) baseline MAP value for at least 1 minute duration
- Number of norepinephrine boluses (0.01 mg) required or, if an infusion is used to maintain MAP equal to or above 65 mmHg, then each time interval of 2 minutes duration of continuous norepinephrine infusion will be counted as one event.
Measured: From start of Investigational Medicinal Product (IMP) administration until 15 minutes after first skin incision
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study start24 Jul 2018
- Primary completion2 Apr 2020
- Study completion2 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anesthesia, IntravenousStudies 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
- 469 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paion UK Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ORION Clinical Services, Simbec Research, Creative Clinical Research GmbH
- Responsible party
- Sponsor
- Investigators
- Jörg Fechner, Prof. Dr., Principal investigator, University Erlangen-Nürnberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03661489
- Sponsor's protocol ID
- CNS7056-022
- Status last verified
- May 2020
- First submitted
- 3 Sep 2018
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20.
PubMed 22190555Wiltshire HR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation. Anesth Analg. 2012 Aug;115(2):284-96. doi: 10.1213/ANE.0b013e318241f68a. Epub 2012 Jan 16.
PubMed 22253270
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Confirmatory Efficacy and Safety Trial of Remimazolam (CNS7056) Compared With Propofol for Intravenous Anesthesia During Elective Surgery in ASA Class III/IV Patients
- ClinicalTrials.gov ID
- NCT03661489
- Acronym / sponsor ID
- CNS7056-022
- Conditions
- Anesthesia, Intravenous
- Keywords
- remimazolam
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 469 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- ORION Clinical Services, Simbec Research, Creative Clinical Research GmbH
- Study start
- 24 Jul 2018 (actual)
- Primary completion
- 2 Apr 2020 (actual)
- Study completion
- 2 Apr 2020 (actual)
- First posted
- 7 Sep 2018 (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.
A phase III confirmatory trial evaluating the efficacy and safety of remimazolam (CNS7056) compared to propofol for intravenous anesthesia during elective surgery in ASA Class III/IV patients.
Detailed description
This is a Phase III single-blind, randomized, controlled, non-inferiority multi-center trial in American Society of Anesthesiologists (ASA) Class III/IV patients undergoing elective surgery, comparing remimazolam to propofol for induction and maintenance of intravenous anesthesia. In accordance with general anesthetic standard regimen, remimazolam or propofol, will be administered together with remifentanil as analgesic agent, and with a neuromuscular blocker to facilitate intubation and achieve muscle relaxation
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Remimazolam 50 mg | Experimental | Drug: RemimazolamFor induction of general anesthesia, remimazolam is co-administered with remifentanil for analgesia and with a muscle relaxant as necessary. For maintenance of general anesthesia remimazolam is titrated to effect. Administration of boluses of remimazolam is allowed. Remifentanil is continued and/or titrated. Boluses of muscle relaxants are given throughout the surgical procedure as needed. |
| Intravenous Propofol 2% | Active comparator | Drug: PropofolFor induction of general anesthesia, propofol is co-administered with remifentanil for analgesia and with a muscle relaxant as necessary. For maintenance of general anesthesia propofol is titrated to effect. Administration of boluses of propofol is allowed. Remifentanil is continued and/or titrated. Boluses of muscle relaxants are given throughout the surgical procedure as needed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female ASA III/IV patients at least 18 years old, scheduled for an elective surgical procedure of a minimum duration of approximately 90 minutes under general anesthesia (GA) and planned to be extubated immediately post-operatively.
- Total intravenous GA with the requirement for mechanical ventilation via endotracheal tube and necessary invasive blood pressure (BP) monitoring either due to severity of illness, severity of concomitant diseases, type of surgery or decisions of the anesthesia staff.
- Patients scheduled to stay in the hospital long enough after the surgical procedure to perform all trial follow-up procedures (~1 day)
- For female patients of childbearing potential: Negative result of a pregnancy test taken shortly before the start of the administration of the IMP as well as consent to use highly effective birth control from the last menstrual cycle prior to the start of the IMP until the end of the trial follow-up procedures. Highly effective methods of birth control include:
- Women who had their last menstruation at least two years ago or who underwent surgical interventions (surgical birth control, bilateral oophorectomy, hysterectomy, etc.) are regarded as having no childbearing potential
Key exclusion criteria (18 listed)
- Patients scheduled for spinal anesthesia, epidural anesthesia (central neuraxial anesthesia) or regional anesthesia. The placement of a peridural catheter with a test dose application of a local anesthetic drug (up to 5 mL) to verify correct positioning to achieve post-operative analgesia and the regional administration of local anesthetic for post-operative analgesia after wound closure is accepted.
- Patients undergoing transplant surgery, cardiac surgery, or intracranial neurosurgery, patients which have to be in prone position for surgery, emergency surgery, or any surgical procedure with the need for or scheduled for post-operative ventilator support.
- Patients undergoing surgical procedures that require keeping the BP at a high level, e.g. surgical procedures in beach chair position
- Patients with severe hypertension, i.e., one baseline result of systolic BP 200 mmHg or more and / or diastolic BP of 120 mmHg or more. Baseline is defined as the time after signature of the informed consent form (ICF) and before arrival in the operating room (OR) suite.
- Patients with total bilirubin of ≥3.0 mg/dL or ≥3 times increase in aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) than the institutional reference range in laboratory tests, or any other laboratory results that make the patient unsuitable for the trial. All laboratory tests relevant for subject's enrolment must be performed within 7 days prior to start of IMP*
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 |
|---|---|---|
| RemimazolamFor induction and maintenance of general anesthesia | Drug | Intravenous Remimazolam 50 mg |
| PropofolFor induction and maintenance of general anesthesia | Drug | Intravenous Propofol 2% |
Primary outcome
Percentage (%) of time of Narcotrend Index (NCI) values ≤ 60 during maintenance phase of general anesthesia (defined as time between the first skin incision and the completion of the last skin suture)
Time frame: maintenance phase of general anesthesia (time between the first skin incision and the completion of the last skin suture)
The primary efficacy endpoint (PEP) is the anesthetic effect of remimazolam and propofol assessed as percent (%) of time of NCI ≤60 during the maintenance phase of general anesthesia
1 secondary outcome
Number of events of critical decrease(s) in mean arterial blood pressure (MAP)
Time frame: From start of Investigational Medicinal Product (IMP) administration until 15 minutes after first skin incision
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
- Background: PubMed 22190555Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20.
- Background: PubMed 22253270Wiltshire HR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation. Anesth Analg. 2012 Aug;115(2):284-96. doi: 10.1213/ANE.0b013e318241f68a. Epub 2012 Jan 16.
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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.
Jörg Fechner, Prof. Dr. principal investigator
University Erlangen-Nürnberg
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 Remimazolam and Propofol in people with Anesthesia, Intravenous, 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 18 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: finished, as of the sponsor's last update on 28 May 2020. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage (%) of time of Narcotrend Index (NCI) values ≤ 60 during maintenance phase of general anesthesia (defined as time between the first skin incision and the completion of the last skin suture) (time frame: maintenance phase of general anesthesia (time between the first skin incision and the completion of the last skin suture)). 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 NCT03661489, which also lists 2 linked publications.
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 28 May 2020.