Addition of Hyalase to Local Anesthetic in Scalp BlockEarly Phase 1NCT03411330
Safety and Efficacy of Addition of Hyaluronidase to Lidocaine and Bupivacaine in Scalp Nerves Block in Elective Craniotomy Operations, Comparative Study
A Early Phase 1 study testing Hyaluronidase, Lidocaine and Bupivacaine in people with Addition of Hyalase to Local Anesthetic in Scalp Block, run by Cairo University at 1 site in Egypt.
Trial summary
Safety and efficacy of addition of hyaluronidase to lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations,Comparative study Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Addition of Hyalase to Local Anesthetic in Scalp Block
- What is being tested?
- Hyaluronidase, Lidocaine and Bupivacaine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteEgypt
- Study dates
- 24 Jan 2017to 24 Apr 2018
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- ASA Ι and II.
- Both males and females, age (18-60) years.
- Supine position.
- Glasco coma scale more than 12.
- Elective craniotomy operations.
Who cannot join
- ASA ΙII or IV
- History of allergy to the study drugs.
- Surgery to remove pituitary tumours or affecting pituitary hormones.
- Glasco coma scale less than 12.
- The need for postoperative ventilation.
Trial locations and contacts
1 site in 1 country.
About this study
Safety and efficacy of addition of hyaluronidase to lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations,Comparative study
Read the detailed description
Patients undergoing craniotomy operations are susceptible to many injurious stimuli such as skin incision, insertion of cranial pins, dural incision, dural and skin closure. They cause different levels of nociception and these stimuli can result in sudden increases in blood pressure and heart rate due to triggering stress response.
Strategies to blunt these noxious stimuli and attenuate this stress response include administration of systemic opioids, deepening the level of anaesthesia. Scalp nerves block by local anaesthetics also can be used.
However, most systemically administered medications studied for post-craniotomy pain usually associated with side effects such as sedation, nausea, and vomiting and depressed ventilation such events are particularly important for post-craniotomy patients.
Using regional aesthetic techniques in addition to general anaesthesia have been conducted as multimodality managements for post-craniotomy pain and to decrease systemic administration of analgesics and hence decrease their systemic complications.
The stress response is the hormonal and metabolic changes that follow injury or trauma. This includes wide range of endocrinological and immunological effects. The stress response to surgery is characterized by increased secretion of pituitary hormones and activation of the sympathetic nervous system. Hypothalamic activation of the sympathetic autonomic nervous system results in increased secretion of catecholamines from the adrenal medulla and release of norepinephrine from presynaptic nerve terminals. IL-6 is produced in substantial quantities at the site of a surgical wound.IL-6 enters the circulation, and its concentration correlates with the severity of surgery and thus with the magnitude of the tissue injury. At 24 to 36 h after surgery, the levels of IL-6 in the plasma reach preoperative values, because its production is attenuated. Postoperative pain behaves like wound on plasma IL-6: intense postoperative pain correlates with the magnitude of tissue injury and subsides days after. Pain in the first 24 hours after brain surgery is a significant problem, with 60% to 80% of patients experiencing moderate to severe pain.
Blockade of scalp innervation which anesthetises both the superficial and deep layers of the scalp, was used as a means of decreasing hemodynamic reactions during and after craniotomy operations. Various protocols to control postoperative pain were suggested, including infiltration of the scalp with local anaesthetics. These include the use of 0.5% bupivacaine combined with additional lidocaine 2 %.
Hyaluronidase is a naturally produced enzyme, it's produced by various types of bacteria, and primary helps bacteria to dissolve hyaluronic acid that constitutes major component of the connective tissue substance thus helping spread of other bacterial products. On December 2005, the FDA approved a synthetic (recombinant or rDNA) human hyaluronidase. The addition of hyaluronidase to local anaesthetics has been shown to enhance safely and effectively the diffusion of the drug, thereby increasing the analgesic efficacy especially in the first minutes after injection
- Being tested
- Hyaluronidase, Lidocaine, Bupivacaine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HyaluronidaseDrug
Also called Hyaluronidase with lidocaine and bupivacaine
Scalp nerves block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum allowed dose 175 mg in group A, Hyaluronidase will be added in group H in a dose of 1500 IU (The minimum and maximum effective doses of hyaluronidase are not known. The doses used range from0.75 IU/ml to 300 IU/ml
LidocaineDrug
Also called Lidocaine alone
lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%)
BupivacaineDrug
Also called Bupivacaine alone
bupivacaine (0.5%)
| Study group | Role | What they receive |
|---|---|---|
| Group H (Hyaluronidase added to local anaesthetics) | Active comparator | group H scalp block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum allowed dose 175 mg , Hyaluronidase will be added in in a dose of 1500 IU . The scalp block technique includes infiltrating local anaesthetic to 7 nerves on either side. This is an anatomical block and not just a ring block. At the end of the scalp block further local anesthetic can be infiltrated locally to the pin sites and 7 nernes supraorbital nerve, a branch of the trigeminal nerve,supratrochlear nerve, a branch of the trigeminal nerve.
zygomaticotemporal nerve,auriculotemporal nerve, lesser occipital nerve, greater occipital nerve and greater auricular nerve Receives: Drug: Hyaluronidase; Drug: Lidocaine; Drug: Bupivacaine |
| Group A (local anaesthetics alone) | Active comparator | Group A :scalp nerves block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum dose of 175 mg The scalp block technique includes infiltrating local anaesthetic to 7 nerves on either side. This is an anatomical block, and not just a ring block. At the end of the scalp block; further local anesthetic can be infiltrated locally to the pin sites and 7 nernes Supraorbital nerve, a branch of the trigeminal nerve.
supratrochlear nerve, a branch of the trigeminal nerve. zygomaticotemporal nerve, auriculotemporal nerve, lesser occipital nerve, greater occipital nerve, greater auricular nerve Receives: Drug: Lidocaine; Drug: Bupivacaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-operative pain evaluation
Post-operative VAS for pain post-operative.
Measured: up to 24 hours postoperatively
Secondary outcomes (5)
Haemodynamic Measures
Effects on haemodynamics: Heart rate"beats per minute" intra and post-operative in both groups
Measured: Every 5 minutes during operation In first 24 hours postoperatively
Interleukin 6 measurement
Measurement of level of interleukin 6 as an indicator of inflammatory response and pain
Measured: Interleukin 6 level will be measured before surgery (9:00 A.M),30 minutes after scalp nerves block, 60 minutes after skin incision and after 6 hours post-operative.
Intraoperative rescue dose of opioid
Number of patients requiring intraoperative rescue doses of opioids
Measured: 6 hours postoperative then every 2 hours for 24 hours.
Time of first analgesic request
First time to seek analgesia (time of first analgesic request)
Measured: Intraoperative
Haemodynamic effects
Effects on haemodynamics:, systolic, diastolic and mean arterial blood pressure" mm Hg".
Measured: up to 24 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start24 Jan 2017
- Primary completion22 Apr 2018
- Study completion24 Apr 2018
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 Addition of Hyalase to Local Anesthetic in Scalp BlockStudies of the same condition, open and under way.
- More trials run by Cairo 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The investigators hypothesize that, the addition of hyaluronidase may affect the quality of the block by enhancing the spread of the local anaesthetics through the facial planes and thus, reaching the target nerves more easily, rapid and effective that may provide better effective block in short duration and lasting for longer duration. This effect will be measured in terms of "stress response" and " analgesic quality" Total sample size of 64 patients randomly allocated into two equal groups. According to study "Hyaluronidase in sub-Tenon's anesthesia for phacoemulsification" that was done and published in International Journal of Ophthalmology (2012) to detect difference in post-operative pain between those patients receiving Lidocaine only versus Lidocaine and hyaluronidase, sample size of 29 patients per group is needed with confidence level 95% power of the study 80% \& type I error 0.05. Sample size calculation was done using Medcalc Software version 15.4.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Collaborators
- Mohamed, Ahmed A., M.D., Tarek Ahmed Radwan, Mohamed Mahmoud Mohamed, Hatem Abdellatif Mohamed, Badawy Mohammed Al-Kholy
- Responsible party
- Principal investigator, Ahmed Abdalla, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03411330
- Sponsor's protocol ID
- N-58/2017
- Status last verified
- Apr 2018
- First submitted
- 27 Dec 2017
- Last updated
- 27 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Via scholar Gate
Publications
Mohamed AA, Radwan TA, Mohamed MM, Mohamed HA, Mohamed Elemady MF, Osman SH, Safan TF, Khair TM, Ali NA, Fahmy RS, Belita MI, Abdalla SR, Seleem AA, Atta EM, Zaid OI, Ragab AS, Salem AE, AlKholy BM. Safety and efficacy of addition of hyaluronidase to a mixture of lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations; comparative study. BMC Anesthesiol. 2018 Sep 15;18(1):129. doi: 10.1186/s12871-018-0590-9.
PubMed 30219027
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Addition of Hyaluronidase to Lidocaine and Bupivacaine in Scalp Nerves Block in Elective Craniotomy Operations, Comparative Study
- ClinicalTrials.gov ID
- NCT03411330
- Acronym / sponsor ID
- N-58/2017
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Collaborators
- Mohamed, Ahmed A., M.D., Tarek Ahmed Radwan, Mohamed Mahmoud Mohamed, Hatem Abdellatif Mohamed, Badawy Mohammed Al-Kholy
- Study start
- 24 Jan 2017 (actual)
- Primary completion
- 22 Apr 2018 (actual)
- Study completion
- 24 Apr 2018 (actual)
- First posted
- 26 Jan 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.
Safety and efficacy of addition of hyaluronidase to lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations,Comparative study
Detailed description
Patients undergoing craniotomy operations are susceptible to many injurious stimuli such as skin incision, insertion of cranial pins, dural incision, dural and skin closure. They cause different levels of nociception and these stimuli can result in sudden increases in blood pressure and heart rate due to triggering stress response.
Strategies to blunt these noxious stimuli and attenuate this stress response include administration of systemic opioids, deepening the level of anaesthesia. Scalp nerves block by local anaesthetics also can be used.
However, most systemically administered medications studied for post-craniotomy pain usually associated with side effects such as sedation, nausea, and vomiting and depressed ventilation such events are particularly important for post-craniotomy patients.
Using regional aesthetic techniques in addition to general anaesthesia have been conducted as multimodality managements for post-craniotomy pain and to decrease systemic administration of analgesics and hence decrease their systemic complications.
The stress response is the hormonal and metabolic changes that follow injury or trauma. This includes wide range of endocrinological and immunological effects. The stress response to surgery is characterized by increased secretion of pituitary hormones and activation of the sympathetic nervous system. Hypothalamic activation of the sympathetic autonomic nervous system results in increased secretion of catecholamines from the adrenal medulla and release of norepinephrine from presynaptic nerve terminals. IL-6 is produced in substantial quantities at the site of a surgical wound.IL-6 enters the circulation, and its concentration correlates with the severity of surgery and thus with the magnitude of the tissue injury. At 24 to 36 h after surgery, the levels of IL-6 in the plasma reach preoperative values, because its production is attenuated. Postoperative pain behaves like wound on plasma IL-6: intense postoperative pain correlates with the magnitude of tissue injury and subsides days after. Pain in the first 24 hours after brain surgery is a significant problem, with 60% to 80% of patients experiencing moderate to severe pain.
Blockade of scalp innervation which anesthetises both the superficial and deep layers of the scalp, was used as a means of decreasing hemodynamic reactions during and after craniotomy operations. Various protocols to control postoperative pain were suggested, including infiltration of the scalp with local anaesthetics. These include the use of 0.5% bupivacaine combined with additional lidocaine 2 %.
Hyaluronidase is a naturally produced enzyme, it's produced by various types of bacteria, and primary helps bacteria to dissolve hyaluronic acid that constitutes major component of the connective tissue substance thus helping spread of other bacterial products. On December 2005, the FDA approved a synthetic (recombinant or rDNA) human hyaluronidase. The addition of hyaluronidase to local anaesthetics has been shown to enhance safely and effectively the diffusion of the drug, thereby increasing the analgesic efficacy especially in the first minutes after injection
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- The investigators hypothesize that, the addition of hyaluronidase may affect the quality of the block by enhancing the spread of the local anaesthetics through the facial planes and thus, reaching the target nerves more easily, rapid and effective that may provide better effective block in short duration and lasting for longer duration. This effect will be measured in terms of "stress response" and " analgesic quality" Total sample size of 64 patients randomly allocated into two equal groups. According to study "Hyaluronidase in sub-Tenon's anesthesia for phacoemulsification" that was done and published in International Journal of Ophthalmology (2012) to detect difference in post-operative pain between those patients receiving Lidocaine only versus Lidocaine and hyaluronidase, sample size of 29 patients per group is needed with confidence level 95% power of the study 80% \& type I error 0.05. Sample size calculation was done using Medcalc Software version 15.4.
| Arm | Type | Receives |
|---|---|---|
| Group H (Hyaluronidase added to local anaesthetics) | Active comparator | Drug: Hyaluronidase, Drug: Lidocaine, Drug: Bupivacainegroup H scalp block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum allowed dose 175 mg , Hyaluronidase will be added in in a dose of 1500 IU . The scalp block technique includes infiltrating local anaesthetic to 7 nerves on either side. This is an anatomical block and not just a ring block. At the end of the scalp block further local anesthetic can be infiltrated locally to the pin sites and 7 nernes supraorbital nerve, a branch of the trigeminal nerve,supratrochlear nerve, a branch of the trigeminal nerve. zygomaticotemporal nerve,auriculotemporal nerve, lesser occipital nerve, greater occipital nerve and greater auricular nerve |
| Group A (local anaesthetics alone) | Active comparator | Drug: Lidocaine, Drug: BupivacaineGroup A :scalp nerves block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum dose of 175 mg The scalp block technique includes infiltrating local anaesthetic to 7 nerves on either side. This is an anatomical block, and not just a ring block. At the end of the scalp block; further local anesthetic can be infiltrated locally to the pin sites and 7 nernes Supraorbital nerve, a branch of the trigeminal nerve. supratrochlear nerve, a branch of the trigeminal nerve. zygomaticotemporal nerve, auriculotemporal nerve, lesser occipital nerve, greater occipital nerve, greater auricular nerve |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- ASA Ι and II.
- Both males and females, age (18-60) years.
- Supine position.
- Glasco coma scale more than 12.
- Elective craniotomy operations.
Key exclusion criteria (5 listed)
- ASA ΙII or IV
- History of allergy to the study drugs.
- Surgery to remove pituitary tumours or affecting pituitary hormones.
- Glasco coma scale less than 12.
- The need for postoperative ventilation.
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 |
|---|---|---|
| HyaluronidaseAlso: Hyaluronidase with lidocaine and bupivacaineScalp nerves block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum allowed dose 175 mg in group A, Hyaluronidase will be added in group H in a dose of 1500 IU (The minimum and maximum effective doses of hyaluronidase are not known. The doses used range from0.75 IU/ml to 300 IU/ml | Drug | Group H (Hyaluronidase added to local anaesthetics) |
| LidocaineAlso: Lidocaine alonelidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) | Drug | Group A (local anaesthetics alone), Group H (Hyaluronidase added to local anaesthetics) |
| BupivacaineAlso: Bupivacaine alonebupivacaine (0.5%) | Drug | Group A (local anaesthetics alone), Group H (Hyaluronidase added to local anaesthetics) |
Primary outcome
Post-operative pain evaluation
Time frame: up to 24 hours postoperatively
Post-operative VAS for pain post-operative.
5 secondary outcomes
Haemodynamic Measures
Time frame: Every 5 minutes during operation In first 24 hours postoperatively
Interleukin 6 measurement
Time frame: Interleukin 6 level will be measured before surgery (9:00 A.M),30 minutes after scalp nerves block, 60 minutes after skin incision and after 6 hours post-operative.
Intraoperative rescue dose of opioid
Time frame: 6 hours postoperative then every 2 hours for 24 hours.
Time of first analgesic request
Time frame: Intraoperative
Haemodynamic effects
Time frame: up to 24 hours postoperatively
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 27 Apr 2018.
- Derived from this study: PubMed 30219027Mohamed AA, Radwan TA, Mohamed MM, Mohamed HA, Mohamed Elemady MF, Osman SH, Safan TF, Khair TM, Ali NA, Fahmy RS, Belita MI, Abdalla SR, Seleem AA, Atta EM, Zaid OI, Ragab AS, Salem AE, AlKholy BM. Safety and efficacy of addition of hyaluronidase to a mixture of lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations; comparative study. BMC Anesthesiol. 2018 Sep 15;18(1):129. doi: 10.1186/s12871-018-0590-9.
- Individual participant dataSharing planned: No. Via scholar Gate
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Hyaluronidase, Lidocaine and Bupivacaine in people with Addition of Hyalase to Local Anesthetic in Scalp Block, run by Cairo 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 5 inclusion and 5 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 27 Apr 2018. 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?
Post-operative pain evaluation (time frame: up to 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 NCT03411330, 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 27 Apr 2018.