Entropy Device and How Will Muscle Relaxants Affect itEarly Phase 1NCT05097508
Effect of Atracurium and Rocuronium on the State and Response Entropy During Isoflurane Anesthesia
A Early Phase 1 study testing Atracurium Besylate, Rocuronium Bromide and Entropy in people with Entropy Device and How Will Muscle Relaxants Affect it, run by Ain Shams University at 1 site in Egypt.
Trial summary
Many studies have explored the effects of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but most did not monitor the degree of neuromuscular block. Read more about this study
- Who is it for?
- Ages 20 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Entropy Device and How Will Muscle Relaxants Affect it
- What is being tested?
- Atracurium Besylate, Rocuronium Bromide and Entropy
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteEgypt
- Study dates
- 20 Jun 2020to 1 Oct 2021
- Phase
- Early Phase 1
- 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 20 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients American Society of Anesthesiologists physical status (ASA) I to II.
- Male patients (to avoid bias between gender).
- Age between 20-50 years
Who cannot join
- a. Patients receiving any neuropsychiatric medications. b. Patients undergoing neurosurgical operation. c. Drug addiction. d. Body mass index (BMI) more than or equal to 40.
Trial locations and contacts
1 site in 1 country.
About this study
Many studies have explored the effects of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but most did not monitor the degree of neuromuscular block. In addition, they do not explore the effects of different degrees of neuromuscular blockade on spectral entropy under different concentrations of isoflurane inhalation. Therefore, the present study will evaluate different levels of MAC to quantify the isoflurane concentration, as well as different degrees of neuromuscular blockade
Read the detailed description
The study will include 40 patients fulfilling the inclusion criteria. They will be randomized into 2 equal groups by a computer generated random numbers table, each consisting of 20 patients, namely group A and group R.
- Group A: Patients will receive Atracurium.
- Group R: Patients will receive rocuronium. No premedication will be given. After the patients enter the operating room, a venous cannula will be inserted into a large peripheral vein. Data from routine monitoring, including non-invasive arterial blood pressure, oxygen saturation, and end-tidal oxygen concentration (ETO2) and end-tidal carbon dioxide concentration (ETCO2) will be collected. Neuromuscular blockade will be continuously assessed by acceleromyography using the Train-of-Four-watch SX system (made in Ireland), starting when the patients will be unconscious. RE and SE will be monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system (made in finland).
Baseline RE and SE will be recorded. Anesthesia will be induced by propofol (dose 2-3 mg/kg) and fentanyl as analgesia (dose 1-2 mg/kg). Tracheal intubation will be facilitated with rocuronium (dose 0.6 mg/kg) /atracurium (dose 0.5 mg/kg) after an acceleromyography count of 0. Anesthesia will be maintained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation will be maintained at a tidal volume of 5-7 ml/kg. Ventilator frequency will be adjusted for maintenance of an ETCO2 of 35-40 mmHg. After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Rocuronium (dose 0.01-0.012 mg/kg/min ) /atracurium (dose 0.005-0.01 mg/kg/min) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery.
- Being tested
- Atracurium Besylate, Rocuronium Bromide, Entropy, train of four
- Keywords
- entropy, atracurium, rocuronium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atracurium BesylateDrug
Also called Tracium
Anesthesia will be induced by atracurium (dose 0.5 mg/kg).After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Atracurium (dose 0.005-0.01 mg/kg/min) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. In case of hypotension (drop of blood pressure ˃20% of baseline reading), 10-30 mg of ephedrine diluted over 10 ml normal saline 0.9% will be given intravenously by titration according to the blood pressure. In case of bradycardia (heart rate less than 60 beat per minute), when it is associated with hypotension or any signs of impaired perfusion, 0.01 - 0.02 mg/kg of atropine will be given
Rocuronium BromideDrug
Also called Esmeron
Anesthesia will be induced by rocuronium (dose 0.6 mg/kg).After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Rocuronium (dose 0.01-0.012 mg/kg/min ) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. In case of hypotension (drop of blood pressure ˃20% of baseline reading), 10-30 mg of ephedrine diluted over 10 ml normal saline 0.9% will be given intravenously by titration according to the blood pressure. In case of bradycardia (heart rate less than 60 beat per minute), when it is associated with hypotension or any signs of impaired perfusion, 0.01 - 0.02 mg/kg of atropine will be given.
EntropyDevice
No premedication will be given. After the patients enter the operating room, a venous cannula will be inserted into a large peripheral vein. Data from routine monitoring, including non-invasive arterial blood pressure, oxygen saturation, and end-tidal oxygen concentration (ETO2) and end-tidal carbon dioxide concentration (ETCO2) will be collected. Neuromuscular blockade will be continuously assessed by acceleromyography using the Train-of-Four-watch SX system , starting when the patients will be unconscious. RE and SE will be monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system.
train of fourDevice
After the patients enter the operating room, a venous cannula will be inserted into a large peripheral vein. Data from routine monitoring, including non-invasive arterial blood pressure, oxygen saturation, and end-tidal oxygen concentration (ETO2) and end-tidal carbon dioxide concentration (ETCO2) will be collected. Neuromuscular blockade will be continuously assessed by acceleromyography using the Train-of-Four-watch SX system, starting when the patients will be unconscious. RE and SE will be monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Patients will receive Atracurium. | Experimental | Baseline RE and SE will be recorded. Anesthesia will be induced by propofol (dose 2-3 mg/kg) and fentanyl as analgesia (dose 1-2 mg/kg). Tracheal intubation will be facilitated with atracurium (dose 0.5 mg/kg) after an acceleromyography count of 0. Anesthesia will be maintained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation will be maintained at a tidal volume of 5-7 ml/kg. Ventilator frequency will be adjusted for maintenance of an ETCO2 of 35-40 mmHg. After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Atracurium (dose 0.005-0.01 mg/kg/min) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. Receives: Drug: Atracurium Besylate; Device: Entropy; Device: train of four |
| Group R: Patients will receive rocuronium. | Experimental | Baseline RE and SE will be recorded. Anesthesia will be induced by propofol (dose 2-3 mg/kg) and fentanyl as analgesia (dose 1-2 mg/kg). Tracheal intubation will be facilitated with rocuronium (dose 0.6 mg/kg) after an acceleromyography count of 0. Anesthesia will be maintained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation will be maintained at a tidal volume of 5-7 ml/kg. Ventilator frequency will be adjusted for maintenance of an ETCO2 of 35-40 mmHg. After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Rocuronium (dose 0.01-0.012 mg/kg/min ) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. Receives: Drug: Rocuronium Bromide; Device: Entropy; Device: train of four |
What is being measured
The primary outcome is the main question the study is designed to answer.
to evaluate the impact of different degrees of neuromuscular blockade on SE, RE, and RE-SE difference during isoflurane anesthesia.
to measure effect of atracurium and rocuronium on entropy readings(state,respose and difference between them) during isoflurane anesthesia
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2021
- Study start20 Jun 2020
- Primary completion20 Jun 2021
- Study completion1 Oct 2021
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 Entropy Device and How Will Muscle Relaxants Affect itStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe 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
- Early Phase 1
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- * Group A: Patients will receive Atracurium. * Group R: Patients will receive rocuronium.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Noran Essam Mohamed Hassanien, Ain Shams University
- Investigators
- Noran Hassanien, Principal investigator, AinShams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05097508
- Sponsor's protocol ID
- Noran Hassanien
- Status last verified
- Oct 2021
- First submitted
- 5 Oct 2021
- Last updated
- 28 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all collecting IPD will be shared
Publications
Xing Y, Xu D, Xu Y, Chen L, Wang H, Li S. Effects of Neuromuscular Blockages on Entropy Monitoring During Sevoflurane Anesthesia. Med Sci Monit. 2019 Nov 15;25:8610-8617. doi: 10.12659/MSM.917879.
PubMed 31729355
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Atracurium and Rocuronium on the State and Response Entropy During Isoflurane Anesthesia
- ClinicalTrials.gov ID
- NCT05097508
- Acronym / sponsor ID
- Noran Hassanien
- Keywords
- entropy, atracurium, rocuronium
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 20 Jun 2020 (actual)
- Primary completion
- 20 Jun 2021 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 28 Oct 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.
Many studies have explored the effects of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but most did not monitor the degree of neuromuscular block. In addition, they do not explore the effects of different degrees of neuromuscular blockade on spectral entropy under different concentrations of isoflurane inhalation. Therefore, the present study will evaluate different levels of MAC to quantify the isoflurane concentration, as well as different degrees of neuromuscular blockade
Detailed description
The study will include 40 patients fulfilling the inclusion criteria. They will be randomized into 2 equal groups by a computer generated random numbers table, each consisting of 20 patients, namely group A and group R.
- Group A: Patients will receive Atracurium.
- Group R: Patients will receive rocuronium. No premedication will be given. After the patients enter the operating room, a venous cannula will be inserted into a large peripheral vein. Data from routine monitoring, including non-invasive arterial blood pressure, oxygen saturation, and end-tidal oxygen concentration (ETO2) and end-tidal carbon dioxide concentration (ETCO2) will be collected. Neuromuscular blockade will be continuously assessed by acceleromyography using the Train-of-Four-watch SX system (made in Ireland), starting when the patients will be unconscious. RE and SE will be monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system (made in finland).
Baseline RE and SE will be recorded. Anesthesia will be induced by propofol (dose 2-3 mg/kg) and fentanyl as analgesia (dose 1-2 mg/kg). Tracheal intubation will be facilitated with rocuronium (dose 0.6 mg/kg) /atracurium (dose 0.5 mg/kg) after an acceleromyography count of 0. Anesthesia will be maintained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation will be maintained at a tidal volume of 5-7 ml/kg. Ventilator frequency will be adjusted for maintenance of an ETCO2 of 35-40 mmHg. After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Rocuronium (dose 0.01-0.012 mg/kg/min ) /atracurium (dose 0.005-0.01 mg/kg/min) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- * Group A: Patients will receive Atracurium. * Group R: Patients will receive rocuronium.
| Arm | Type | Receives |
|---|---|---|
| Group A: Patients will receive Atracurium. | Experimental | Drug: Atracurium Besylate, Device: Entropy, Device: train of fourBaseline RE and SE will be recorded. Anesthesia will be induced by propofol (dose 2-3 mg/kg) and fentanyl as analgesia (dose 1-2 mg/kg). Tracheal intubation will be facilitated with atracurium (dose 0.5 mg/kg) after an acceleromyography count of 0. Anesthesia will be maintained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation will be maintained at a tidal volume of 5-7 ml/kg. Ventilator frequency will be adjusted for maintenance of an ETCO2 of 35-40 mmHg. After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Atracurium (dose 0.005-0.01 mg/kg/min) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. |
| Group R: Patients will receive rocuronium. | Experimental | Drug: Rocuronium Bromide, Device: Entropy, Device: train of fourBaseline RE and SE will be recorded. Anesthesia will be induced by propofol (dose 2-3 mg/kg) and fentanyl as analgesia (dose 1-2 mg/kg). Tracheal intubation will be facilitated with rocuronium (dose 0.6 mg/kg) after an acceleromyography count of 0. Anesthesia will be maintained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation will be maintained at a tidal volume of 5-7 ml/kg. Ventilator frequency will be adjusted for maintenance of an ETCO2 of 35-40 mmHg. After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Rocuronium (dose 0.01-0.012 mg/kg/min ) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Patients American Society of Anesthesiologists physical status (ASA) I to II.
- Male patients (to avoid bias between gender).
- Age between 20-50 years
Key exclusion criteria (1 listed)
- a. Patients receiving any neuropsychiatric medications. b. Patients undergoing neurosurgical operation. c. Drug addiction. d. Body mass index (BMI) more than or equal to 40.
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 |
|---|---|---|
| Atracurium BesylateAlso: TraciumAnesthesia will be induced by atracurium (dose 0.5 mg/kg).After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Atracurium (dose 0.005-0.01 mg/kg/min) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. In case of hypotension (drop of blood pressure ˃20% of baseline reading), 10-30 mg of ephedrine diluted over 10 ml normal saline 0.9% will be given intravenously by titration according to the blood pressure. In case of bradycardia (heart rate less than 60 beat per minute), when it is associated with hypotension or any signs of impaired perfusion, 0.01 - 0.02 mg/kg of atropine will be given | Drug | Group A: Patients will receive Atracurium. |
| Rocuronium BromideAlso: EsmeronAnesthesia will be induced by rocuronium (dose 0.6 mg/kg).After equilibrium for 30 minutes SE, RE and the difference between them will be recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF value of 50% and 100%. Rocuronium (dose 0.01-0.012 mg/kg/min ) will be administered as a continuous IV infusion adjusted until 50% and 100% depression of T1 ( first twitch by acceleromyography) will be observed. The entire experiment ended before the start of surgery. In case of hypotension (drop of blood pressure ˃20% of baseline reading), 10-30 mg of ephedrine diluted over 10 ml normal saline 0.9% will be given intravenously by titration according to the blood pressure. In case of bradycardia (heart rate less than 60 beat per minute), when it is associated with hypotension or any signs of impaired perfusion, 0.01 - 0.02 mg/kg of atropine will be given. | Drug | Group R: Patients will receive rocuronium. |
| EntropyNo premedication will be given. After the patients enter the operating room, a venous cannula will be inserted into a large peripheral vein. Data from routine monitoring, including non-invasive arterial blood pressure, oxygen saturation, and end-tidal oxygen concentration (ETO2) and end-tidal carbon dioxide concentration (ETCO2) will be collected. Neuromuscular blockade will be continuously assessed by acceleromyography using the Train-of-Four-watch SX system , starting when the patients will be unconscious. RE and SE will be monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system. | Device | Group A: Patients will receive Atracurium., Group R: Patients will receive rocuronium. |
| train of fourAfter the patients enter the operating room, a venous cannula will be inserted into a large peripheral vein. Data from routine monitoring, including non-invasive arterial blood pressure, oxygen saturation, and end-tidal oxygen concentration (ETO2) and end-tidal carbon dioxide concentration (ETCO2) will be collected. Neuromuscular blockade will be continuously assessed by acceleromyography using the Train-of-Four-watch SX system, starting when the patients will be unconscious. RE and SE will be monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system. | Device | Group A: Patients will receive Atracurium., Group R: Patients will receive rocuronium. |
Primary outcome
to evaluate the impact of different degrees of neuromuscular blockade on SE, RE, and RE-SE difference during isoflurane anesthesia.
Time frame: 1 year
to measure effect of atracurium and rocuronium on entropy readings(state,respose and difference between them) during isoflurane anesthesia
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 Oct 2021.
- Results publication: PubMed 31729355Xing Y, Xu D, Xu Y, Chen L, Wang H, Li S. Effects of Neuromuscular Blockages on Entropy Monitoring During Sevoflurane Anesthesia. Med Sci Monit. 2019 Nov 15;25:8610-8617. doi: 10.12659/MSM.917879.
- Individual participant dataSharing planned: Yes. all collecting IPD will be shared
Related trials for Entropy Device and How Will Muscle Relaxants Affect it
Recruiting
Impact of Entropy Monitoring on Anesthetic Consumption and Recovery After Laparoscopic Cholecystectomy
Entropy Device and How Will Muscle Relaxants Affect it
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.
Noran Hassanien principal investigator
AinShams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Atracurium Besylate, Rocuronium Bromide and Entropy in people with Entropy Device and How Will Muscle Relaxants Affect it, run by Ain Shams University at 1 site in Egypt.
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 3 inclusion and 1 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 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 Egypt. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
to evaluate the impact of different degrees of neuromuscular blockade on SE, RE, and RE-SE difference during isoflurane anesthesia. (time frame: 1 year). 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 NCT05097508, 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 28 Oct 2021.