Thalassemia in ChildrenPhase 2NCT05078463
Efficacy of Transdermal Microneedle Patch for Topical Anesthesia Enhancement in Paediatric Thalassemia Patients
A Phase 2 study testing Microneedle, 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time) and 1 Finger Tip Unit (FTU) EMLA (15-minute application time) in people with Thalassemia in Children, run by Universiti Kebangsaan Malaysia Medical Centre at 1 site in Malaysia.
Trial summary
Microneedle (MN) is the mimic of a hypodermic needle, composed of hundreds of micron-sized, out-of-plane protrusions, typically arranged in arrays on a patch that can be applied onto the skin. MN can be fabricated from a variety of materials, preferably biocompatible polymers. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Thalassemia in Children
- What is being tested?
- Microneedle, 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time) and 1 Finger Tip Unit (FTU) EMLA (15-minute application time)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteMalaysia
- Study dates
- 15 Sep 2021to 11 Aug 2022
- Phase
- Phase 2
- 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 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients aged at least 6 to 17 years old
- Patients requiring venous cannulation for blood transfusion
Who cannot join
- Patients with a previous history of sensitization or allergy to EMLA cream
- Patients with a previous history of allergy to materials used in the study (e.g. Polyvinyl Alcohol (PVA), Polyethylene Terephthalate (PET), Maltose, Electrodes and Plaster constituents)
- Patients receiving other forms of analgesic agents within 24 hours prior to the cannulation procedures
- Patients with generalized skin disorders / rash
- Patients who are agitated or aggressive
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia (Ukm Medical Centre)
Kuala Lumpur, Kuala Lumpur, 56000
About this study
Official title: Transdermal Microneedle Patch To Enhance Topical Anaesthesia Before Intravenous Line Insertion for Blood Transfusion In Paediatric Thalassemia Patients
Microneedle (MN) is the mimic of a hypodermic needle, composed of hundreds of micron-sized, out-of-plane protrusions, typically arranged in arrays on a patch that can be applied onto the skin. MN can be fabricated from a variety of materials, preferably biocompatible polymers. Maltose, a natural carbohydrate, is a safe and biocompatible product that can be fabricated into MNs that are biodegradable and soluble within minutes. So far, maltose MN efficacy in enhancing the transdermal drug delivery (TDD) of topical anaesthetic agent such as Eutectic Mixture of Local Anesthetics (EMLA) and thus reducing the pain experienced by paediatric thalassemic patients requiring intravenous cannulation for regular blood transfusion has not been extensively studied. Therefore, the goals of this research are: 1) To compare the VAS score between thalassemic paediatric patients receiving EMLA before IV cannulation for blood transfusion and those receiving EMLA without microneedle application; 2) To compare the skin conductance algesimeter index between those receiving EMLA and microneedle and those receiving EMLA without microneedle application prior to intravenous (IV) cannulation for blood transfusion; 3) To evaluate the agreement between VAS score and the skin conductance algesimeter index obtained via PainMonitor™ machine.
Read the detailed description
This is a prospective, phase II, randomized, double-blind (participants and care providers), cross-over, negative controlled trial.
Prior to the administration of intervention / control, relevant clinic-demographic profiles (age, gender, ethnicity, anthropometric measurements, presence of comorbidities, thalassemia types etc) will be recorded and entered in the case report forms (CRFs) that are specifically designed for this study.
This research study uses Eutectic Mixture of Local Anesthetics (EMLA) Cream (lidocaine 2.5% and prilocaine 2.5%) as the topical anaesthetic agent. EMLA Cream is a eutectic emulsion mixture of lidocaine and prilocaine at 1:1 ratio (i.e. each gram of EMLA cream contains lidocaine and prilocaine, 25 mg each). A eutectic mixture has a lower melting temperature than each constituent's melting temperature. The anaesthetic efficacy of EMLA cream will be assessed via pain induced by intravenous (IV) cannulation and the primary endpoint is the participant's VAS score measured after applying EMLA Cream (with and without MN application) for 15 and 30 minutes.
The window period given to EMLA Cream for its effect to work will be based on the usual clinical practice observation where it is usually applied for 30 minutes prior to IV catheterization. The rationale behind it is due to logistical issues and for the day care's operational convenience. Nevertheless, in a busy clinical setting, the application time is sometimes shortened to 15 minutes for slight anaesthetic effect. Thus, the study investigators postulate that, with the aid of microneedle, the time to onset of action for EMLA Cream could be greatly reduced, thus requiring less time for EMLA cream to achieve its maximal effects.
According to the routine hospital protocol, all study participants received their blood transfusion based on the Good Clinical Practice (GCP) guidelines. For each participant, the individual will be randomized to one of the 24 treatment sequences and there will be a minimum of 3-weeks washout period before administering the next intervention.
The investigator identified and drew a grid of 1cm × 1cm on the dorsum hand, which served as an ideal site for cannulation. The administrator of intervention (procedurist) will apply either 1 Finger Tip Units (FTUs) of EMLA Cream (approximately 0.68g/cm2) or 0.5 Finger Tip Unit (FTU) (approximately 0.369 g/cm2) over the preparation area. If the patient is subjected to MN patching at his/her visit, the MN patch will be applied by thumb force with the pillar handler pressed firmly against the dorsal hand surface for 5 seconds, mimicking a stamping action, to patch MN to the skin entirely before applying EMLA cream. Otherwise, an empty (i.e without MN) PVA-containing PET sham patch will be applied instead. Besides, the height-to-base ratio (4:1) used for MN will also optimally minimise its adverse effects (pain, redness), thus preserving the masking (blinding) of study participants from knowing the types of interventions received. The preparation area will be covered with an adhesive dressing ( 3M™Tegaderm™, Maplewood, Minnesota, USA) after EMLA cream application. After the allocated application time (15 or 30 minutes), the attending medical officer will set up the transfusion line with a 22-gauge hypodermic needle inserted into the dorsum hand. Throughout the process, the parents/guardians will be allowed to stay by the patient's side at all times.
After the intervention is given to the patients, the participants will be guided on the operating manual for a 10-points, 100mm VAS pain score. The participants will be presented with a ruler that contains 100-mm slots with "No Pain" written on the left side and "Worst Pain" on the opposite right side.
After each procedure, the children then will be asked to move and place the slider in the slot that accurately describes his/her pain at the following time points: 1) right after application of MN/ sham patch or before EMLA Cream application (baseline VAS score); 2) one minute after IV cannulation. The investigator will record the location of the slot where the slider is placed in (millimetres (mm), clearly printed on the ruler's backside) and this will be the participant's VAS score. Throughout the process, there will be a trained nurse standing by at the day-care to assist the verification of the pain scale and to aid the participants who require additional assistance.
Besides, before applying MN patch and EMLA Cream, the patients will be attached with the PainMonitor™ (Med-Storm Innovation AS, Oslo, Norway) device whereby the electrodes will be attached to the hypothenar eminence of the opposite hand not receiving the blood transfusion. The skin conductance peaks (in microSiemens (μS) and the average rise time (in microSiemens per second (μS/s)) will be recorded. Those parameters indicate the skin's sympathetic nerve block induced by the applied EMLA cream.
For skin conductance algesimeter index, the readings right after MN / sham patch application (baseline skin conductance algesimeter index score) and one minute IV cannulation will be obtained from the PainMonitor™ machine.
- Conditions
- Thalassemia in Children
- Being tested
- Microneedle, 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time), 1 Finger Tip Unit (FTU) EMLA (15-minute application time), 0.5 Finger Tip Unit (FTU) EMLA (30-minute application time), Sham Patch
- Keywords
- Microneedle, Maltose Microneedle, Thalassemia in Children, Paediatric Thalassemia, Transdermal microneedle patch, EMLA, Intravenous cannulation, Blood transfusion, Intravenous line insertion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicroneedleDevice
Also called Maltose Microneedle Array Patch, Maltose Microneedle Patch
Maltose Microneedle Patch (Patch Size: 1 cm x 1 cm, 36 microneedles per patch, microneedle's height, base width and tip radius are 400 μm, 100 μm and 3 μm, respectively) will be firmly applied for 5 seconds on the 1 cm x 1 cm site for IV cannulation on the dorsal surface of the hand for blood transfusion, prior to EMLA cream application.
1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time)Drug
Also called EMLA topical cream
1 Finger Tip Units (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion
1 Finger Tip Unit (FTU) EMLA (15-minute application time)Drug
Also called EMLA topical cream
1 Finger Tip Unit (FTU) EMLA applied for 15 minutes on the dorsal surface of the IV cannulated hand
0.5 Finger Tip Unit (FTU) EMLA (30-minute application time)Drug
Also called EMLA topical cream
0.5 Finger Tip Unit (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion
Sham PatchDevice
Also called Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham Patch
A Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham Patch of a size of 1cm x 1cm will be applied for 5 seconds against the pre-specified 1 cm x 1 cm grid on the dorsal surface of the IV cannulated hand for blood transfusion.
| Study group | Role | What they receive |
|---|---|---|
| Intervention A: Microneedle with 1 Finger Tip Unit (FTU) EMLA for 30 minutes | Experimental | A Maltose Microneedle array patch (size: 1 cm x 1 cm) containing 36 microneedles (the height, base width and tip radius of each microneedle are 400 μm, 100 μm and 3 μm, respectively) with 1 mm needle gap in between will be firmly applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. 1 Finger Tip Unit (FTU) of EMLA cream (containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5%) (approximately 0.68g/cm2) will then be topically applied for 30 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. Receives: Device: Microneedle; Drug: 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time) |
| Intervention B: Microneedle with 0.5 Finger Tip Unit (FTU) EMLA for 30 minutes | Experimental | A Maltose Microneedle array patch (size: 1 cm x 1 cm) containing 36 microneedles (the height, base width and tip radius of each microneedle are 400 μm, 100 μm and 3 μm, respectively) with 1 mm needle gap in between will be firmly applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. 0.5 Finger Tip Unit (FTU) of EMLA cream containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5% (dose: approximately 0.369 g/cm2) will then be topically applied for 30 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. Receives: Device: Microneedle; Drug: 0.5 Finger Tip Unit (FTU) EMLA (30-minute application time) |
| Intervention C: Microneedle with 1 Finger Tip Units (FTUs) EMLA for 15 minutes | Experimental | A Maltose Microneedle array patch (size: 1 cm x 1 cm) containing 36 microneedles (the height, base width and tip radius of each microneedle are 400 μm, 100 μm and 3 μm, respectively) with1 mm needle gap in between will be firmly applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. One (1) Finger Tip Unit (FTU) of EMLA cream (containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5%) (approximately 0.68g/cm2) will then be topically applied for 15 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. Receives: Device: Microneedle; Drug: 1 Finger Tip Unit (FTU) EMLA (15-minute application time) |
| Intervention D: 1 Finger Tip Unit (FTUs) EMLA only and PVA-containing PET Sham Patch | Sham comparator | A Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham Patch of 1 cm x 1cm size will be applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. One (1) Finger Tip Unit (FTU) of EMLA cream (containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5%) (approximately 0.68g/cm2) will then be topically applied for 30 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. Receives: Drug: 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time); Device: Sham Patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analogue Score (VAS)
VAS score is measured in a continuous scale (range 0-100). It is obtained using a Med-05-100 VAS Pain Scale ruler (Schlenker Enterprises Ltd, Lombard, USA) with 0-100 mm slider. It is measured based on the pain experienced on the IV cannulated hand for blood transfusion. Higher VAS score indicates greater intensity or degree of pain whilst lower VAS score indicates lesser pain intensity.
Measured: The measurements will be made at 1 minute after IV cannulation which will be inserted following EMLA (with or without microneedle) application
Skin Conductance Algesimeter Index
The skin conductance peaks per second, measured in microSiemens per second (μS/s), is obtained using PainMonitor™ (Med-Storm Innovation AS, Oslo, Norway) device on the hypothenar eminence of the opposite hand not receiving blood transfusion. Higher skin conductance algesimeter index indicates greater pain intensity and lower values indicate lesser pain intensity.
Measured: The measurements will be made at 1 minute after IV cannulation which will be inserted following EMLA (with our without microneedle) application
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2021
- Study start15 Sep 2021
- Primary completion11 Aug 2022
- Study completion11 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Thalassemia in ChildrenStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiti Kebangsaan Malaysia Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Institue of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia, Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI)
- Responsible party
- Sponsor
- Investigators
- FOOK-CHOE CHEAH, MD, MRCPCH, PhD, Principal investigator, HOSPITAL CANSELOR TUANKU MUHRIZ, UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTERAZRUL A HAMZAN, BSc, PhD, Principal investigator, INSTITUTE OF MICROENGINEERING AND ELECTRONICS (IMEN), UKMCHANG FU DEE, BSc, PhD, Principal investigator, INSTITUTE OF MICROENGINEERING AND ELECTRONICS (IMEN), UKMXIN YUN CHUA, BSc, Principal investigator, HOSPITAL CANSELOR TUANKU MUHRIZ, UKM (UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTRE)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05078463
- Sponsor's protocol ID
- UKM PPI/111/8/JEP-2021-578
- Other IDs
- PRGS/2/2020/TK05/UKM/01/1
- Status last verified
- Aug 2022
- First submitted
- 20 Sep 2021
- Last updated
- 2 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual Participant Data (IPD) with information such as date of birth, hospital registration number and others that may lead to patient identification removed will be shared via Harvard Dataverse Repository after the end of trial and data collection.
Publications
Waghule T, Singhvi G, Dubey SK, Pandey MM, Gupta G, Singh M, Dua K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomed Pharmacother. 2019 Jan;109:1249-1258. doi: 10.1016/j.biopha.2018.10.078. Epub 2018 Nov 9.
PubMed 30551375Tucak A, Sirbubalo M, Hindija L, Rahic O, Hadziabdic J, Muhamedagic K, Cekic A, Vranic E. Microneedles: Characteristics, Materials, Production Methods and Commercial Development. Micromachines (Basel). 2020 Oct 27;11(11):961. doi: 10.3390/mi11110961.
PubMed 33121041Mooney K, McElnay JC, Donnelly RF. Children's views on microneedle use as an alternative to blood sampling for patient monitoring. Int J Pharm Pract. 2014 Oct;22(5):335-44. doi: 10.1111/ijpp.12081. Epub 2013 Dec 6.
PubMed 24308565Pires LR, Vinayakumar KB, Turos M, Miguel V, Gaspar J. A Perspective on Microneedle-Based Drug Delivery and Diagnostics in Paediatrics. J Pers Med. 2019 Nov 15;9(4):49. doi: 10.3390/jpm9040049.
PubMed 31731656Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012 Nov;64(14):1547-68. doi: 10.1016/j.addr.2012.04.005. Epub 2012 May 1.
PubMed 22575858de Waard-van der Spek FB, van den Berg GM, Oranje AP. EMLA cream: an improved local anesthetic. Review of current literature. Pediatr Dermatol. 1992 Jun;9(2):126-31. doi: 10.1111/j.1525-1470.1992.tb01228.x. No abstract available.
PubMed 1603740Houck CS, Sethna NF. Transdermal analgesia with local anesthetics in children: review, update and future directions. Expert Rev Neurother. 2005 Sep;5(5):625-34. doi: 10.1586/14737175.5.5.625.
PubMed 16162086Duarah S, Sharma M, Wen J. Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population. Eur J Pharm Biopharm. 2019 Mar;136:48-69. doi: 10.1016/j.ejpb.2019.01.005. Epub 2019 Jan 8.
PubMed 30633972Ita K. Transdermal Delivery of Drugs with Microneedles-Potential and Challenges. Pharmaceutics. 2015 Jun 29;7(3):90-105. doi: 10.3390/pharmaceutics7030090.
PubMed 26131647Ali R, Mehta P, Arshad MS, Kucuk I, Chang MW, Ahmad Z. Transdermal Microneedles-A Materials Perspective. AAPS PharmSciTech. 2019 Dec 5;21(1):12. doi: 10.1208/s12249-019-1560-3.
PubMed 31807980Caffarel-Salvador E, Tuan-Mahmood TM, McElnay JC, McCarthy HO, Mooney K, Woolfson AD, Donnelly RF. Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations. Int J Pharm. 2015 Jul 15;489(1-2):158-69. doi: 10.1016/j.ijpharm.2015.04.076. Epub 2015 May 1.
PubMed 25940042Kolli CS, Banga AK. Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm Res. 2008 Jan;25(1):104-13. doi: 10.1007/s11095-007-9350-0. Epub 2007 Jun 28.
PubMed 17597381Taddio A, Ohlsson A, Einarson TR, Stevens B, Koren G. A systematic review of lidocaine-prilocaine cream (EMLA) in the treatment of acute pain in neonates. Pediatrics. 1998 Feb;101(2):E1. doi: 10.1542/peds.101.2.e1.
PubMed 9445511Beltramini A, Milojevic K, Pateron D. Pain Assessment in Newborns, Infants, and Children. Pediatr Ann. 2017 Oct 1;46(10):e387-e395. doi: 10.3928/19382359-20170921-03.
PubMed 29019634Storm H. Changes in skin conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin Anaesthesiol. 2008 Dec;21(6):796-804. doi: 10.1097/ACO.0b013e3283183fe4.
PubMed 18997532
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transdermal Microneedle Patch To Enhance Topical Anaesthesia Before Intravenous Line Insertion for Blood Transfusion In Paediatric Thalassemia Patients
- ClinicalTrials.gov ID
- NCT05078463
- Acronym / sponsor ID
- UKM PPI/111/8/JEP-2021-578
- Conditions
- Thalassemia in Children
- Keywords
- Microneedle, Maltose Microneedle, Thalassemia in Children, Paediatric Thalassemia, Transdermal microneedle patch, EMLA, Intravenous cannulation, Blood transfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Universiti Kebangsaan Malaysia Medical CentreUniversity, hospital or other
- Collaborators
- Institue of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia, Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI)
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 11 Aug 2022 (actual)
- Study completion
- 11 Aug 2022 (actual)
- First posted
- 14 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.
Microneedle (MN) is the mimic of a hypodermic needle, composed of hundreds of micron-sized, out-of-plane protrusions, typically arranged in arrays on a patch that can be applied onto the skin. MN can be fabricated from a variety of materials, preferably biocompatible polymers. Maltose, a natural carbohydrate, is a safe and biocompatible product that can be fabricated into MNs that are biodegradable and soluble within minutes. So far, maltose MN efficacy in enhancing the transdermal drug delivery (TDD) of topical anaesthetic agent such as Eutectic Mixture of Local Anesthetics (EMLA) and thus reducing the pain experienced by paediatric thalassemic patients requiring intravenous cannulation for regular blood transfusion has not been extensively studied. Therefore, the goals of this research are: 1) To compare the VAS score between thalassemic paediatric patients receiving EMLA before IV cannulation for blood transfusion and those receiving EMLA without microneedle application; 2) To compare the skin conductance algesimeter index between those receiving EMLA and microneedle and those receiving EMLA without microneedle application prior to intravenous (IV) cannulation for blood transfusion; 3) To evaluate the agreement between VAS score and the skin conductance algesimeter index obtained via PainMonitor™ machine.
Detailed description
This is a prospective, phase II, randomized, double-blind (participants and care providers), cross-over, negative controlled trial.
Prior to the administration of intervention / control, relevant clinic-demographic profiles (age, gender, ethnicity, anthropometric measurements, presence of comorbidities, thalassemia types etc) will be recorded and entered in the case report forms (CRFs) that are specifically designed for this study.
This research study uses Eutectic Mixture of Local Anesthetics (EMLA) Cream (lidocaine 2.5% and prilocaine 2.5%) as the topical anaesthetic agent. EMLA Cream is a eutectic emulsion mixture of lidocaine and prilocaine at 1:1 ratio (i.e. each gram of EMLA cream contains lidocaine and prilocaine, 25 mg each). A eutectic mixture has a lower melting temperature than each constituent's melting temperature. The anaesthetic efficacy of EMLA cream will be assessed via pain induced by intravenous (IV) cannulation and the primary endpoint is the participant's VAS score measured after applying EMLA Cream (with and without MN application) for 15 and 30 minutes.
The window period given to EMLA Cream for its effect to work will be based on the usual clinical practice observation where it is usually applied for 30 minutes prior to IV catheterization. The rationale behind it is due to logistical issues and for the day care's operational convenience. Nevertheless, in a busy clinical setting, the application time is sometimes shortened to 15 minutes for slight anaesthetic effect. Thus, the study investigators postulate that, with the aid of microneedle, the time to onset of action for EMLA Cream could be greatly reduced, thus requiring less time for EMLA cream to achieve its maximal effects.
According to the routine hospital protocol, all study participants received their blood transfusion based on the Good Clinical Practice (GCP) guidelines. For each participant, the individual will be randomized to one of the 24 treatment sequences and there will be a minimum of 3-weeks washout period before administering the next intervention.
The investigator identified and drew a grid of 1cm × 1cm on the dorsum hand, which served as an ideal site for cannulation. The administrator of intervention (procedurist) will apply either 1 Finger Tip Units (FTUs) of EMLA Cream (approximately 0.68g/cm2) or 0.5 Finger Tip Unit (FTU) (approximately 0.369 g/cm2) over the preparation area. If the patient is subjected to MN patching at his/her visit, the MN patch will be applied by thumb force with the pillar handler pressed firmly against the dorsal hand surface for 5 seconds, mimicking a stamping action, to patch MN to the skin entirely before applying EMLA cream. Otherwise, an empty (i.e without MN) PVA-containing PET sham patch will be applied instead. Besides, the height-to-base ratio (4:1) used for MN will also optimally minimise its adverse effects (pain, redness), thus preserving the masking (blinding) of study participants from knowing the types of interventions received. The preparation area will be covered with an adhesive dressing ( 3M™Tegaderm™, Maplewood, Minnesota, USA) after EMLA cream application. After the allocated application time (15 or 30 minutes), the attending medical officer will set up the transfusion line with a 22-gauge hypodermic needle inserted into the dorsum hand. Throughout the process, the parents/guardians will be allowed to stay by the patient's side at all times.
After the intervention is given to the patients, the participants will be guided on the operating manual for a 10-points, 100mm VAS pain score. The participants will be presented with a ruler that contains 100-mm slots with "No Pain" written on the left side and "Worst Pain" on the opposite right side.
After each procedure, the children then will be asked to move and place the slider in the slot that accurately describes his/her pain at the following time points: 1) right after application of MN/ sham patch or before EMLA Cream application (baseline VAS score); 2) one minute after IV cannulation. The investigator will record the location of the slot where the slider is placed in (millimetres (mm), clearly printed on the ruler's backside) and this will be the participant's VAS score. Throughout the process, there will be a trained nurse standing by at the day-care to assist the verification of the pain scale and to aid the participants who require additional assistance.
Besides, before applying MN patch and EMLA Cream, the patients will be attached with the PainMonitor™ (Med-Storm Innovation AS, Oslo, Norway) device whereby the electrodes will be attached to the hypothenar eminence of the opposite hand not receiving the blood transfusion. The skin conductance peaks (in microSiemens (μS) and the average rise time (in microSiemens per second (μS/s)) will be recorded. Those parameters indicate the skin's sympathetic nerve block induced by the applied EMLA cream.
For skin conductance algesimeter index, the readings right after MN / sham patch application (baseline skin conductance algesimeter index score) and one minute IV cannulation will be obtained from the PainMonitor™ machine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Intervention A: Microneedle with 1 Finger Tip Unit (FTU) EMLA for 30 minutes | Experimental | Device: Microneedle, Drug: 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time)A Maltose Microneedle array patch (size: 1 cm x 1 cm) containing 36 microneedles (the height, base width and tip radius of each microneedle are 400 μm, 100 μm and 3 μm, respectively) with 1 mm needle gap in between will be firmly applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. 1 Finger Tip Unit (FTU) of EMLA cream (containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5%) (approximately 0.68g/cm2) will then be topically applied for 30 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. |
| Intervention B: Microneedle with 0.5 Finger Tip Unit (FTU) EMLA for 30 minutes | Experimental | Device: Microneedle, Drug: 0.5 Finger Tip Unit (FTU) EMLA (30-minute application time)A Maltose Microneedle array patch (size: 1 cm x 1 cm) containing 36 microneedles (the height, base width and tip radius of each microneedle are 400 μm, 100 μm and 3 μm, respectively) with 1 mm needle gap in between will be firmly applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. 0.5 Finger Tip Unit (FTU) of EMLA cream containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5% (dose: approximately 0.369 g/cm2) will then be topically applied for 30 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. |
| Intervention C: Microneedle with 1 Finger Tip Units (FTUs) EMLA for 15 minutes | Experimental | Device: Microneedle, Drug: 1 Finger Tip Unit (FTU) EMLA (15-minute application time)A Maltose Microneedle array patch (size: 1 cm x 1 cm) containing 36 microneedles (the height, base width and tip radius of each microneedle are 400 μm, 100 μm and 3 μm, respectively) with1 mm needle gap in between will be firmly applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. One (1) Finger Tip Unit (FTU) of EMLA cream (containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5%) (approximately 0.68g/cm2) will then be topically applied for 15 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. |
| Intervention D: 1 Finger Tip Unit (FTUs) EMLA only and PVA-containing PET Sham Patch | Sham comparator | Drug: 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time), Device: Sham PatchA Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham Patch of 1 cm x 1cm size will be applied for 5 seconds against the pre-specified 1 cm x 1 cm grid (which will be the ideal site for intravenous cannulation for blood transfusion) on the dorsal surface of the hand. One (1) Finger Tip Unit (FTU) of EMLA cream (containing an equal amount (25 mg) of lidocaine 2.5% and prilocaine 2.5%) (approximately 0.68g/cm2) will then be topically applied for 30 minutes on the same site of microneedle application. Intravenous cannulation will subsequently be carried out. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Patients aged at least 6 to 17 years old
- Patients requiring venous cannulation for blood transfusion
Key exclusion criteria (5 listed)
- Patients with a previous history of sensitization or allergy to EMLA cream
- Patients with a previous history of allergy to materials used in the study (e.g. Polyvinyl Alcohol (PVA), Polyethylene Terephthalate (PET), Maltose, Electrodes and Plaster constituents)
- Patients receiving other forms of analgesic agents within 24 hours prior to the cannulation procedures
- Patients with generalized skin disorders / rash
- Patients who are agitated or aggressive
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 |
|---|---|---|
| MicroneedleAlso: Maltose Microneedle Array Patch, Maltose Microneedle PatchMaltose Microneedle Patch (Patch Size: 1 cm x 1 cm, 36 microneedles per patch, microneedle's height, base width and tip radius are 400 μm, 100 μm and 3 μm, respectively) will be firmly applied for 5 seconds on the 1 cm x 1 cm site for IV cannulation on the dorsal surface of the hand for blood transfusion, prior to EMLA cream application. | Device | Intervention A: Microneedle with 1 Finger Tip Unit (FTU) EMLA for 30 minutes, Intervention B: Microneedle with 0.5 Finger Tip Unit (FTU) EMLA for 30 minutes, Intervention C: Microneedle with 1 Finger Tip Units (FTUs) EMLA for 15 minutes |
| 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time)Also: EMLA topical cream1 Finger Tip Units (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion | Drug | Intervention A: Microneedle with 1 Finger Tip Unit (FTU) EMLA for 30 minutes, Intervention D: 1 Finger Tip Unit (FTUs) EMLA only and PVA-containing PET Sham Patch |
| 1 Finger Tip Unit (FTU) EMLA (15-minute application time)Also: EMLA topical cream1 Finger Tip Unit (FTU) EMLA applied for 15 minutes on the dorsal surface of the IV cannulated hand | Drug | Intervention C: Microneedle with 1 Finger Tip Units (FTUs) EMLA for 15 minutes |
| 0.5 Finger Tip Unit (FTU) EMLA (30-minute application time)Also: EMLA topical cream0.5 Finger Tip Unit (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion | Drug | Intervention B: Microneedle with 0.5 Finger Tip Unit (FTU) EMLA for 30 minutes |
| Sham PatchAlso: Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham PatchA Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham Patch of a size of 1cm x 1cm will be applied for 5 seconds against the pre-specified 1 cm x 1 cm grid on the dorsal surface of the IV cannulated hand for blood transfusion. | Device | Intervention D: 1 Finger Tip Unit (FTUs) EMLA only and PVA-containing PET Sham Patch |
Primary outcome
Visual Analogue Score (VAS)
Time frame: The measurements will be made at 1 minute after IV cannulation which will be inserted following EMLA (with or without microneedle) application
VAS score is measured in a continuous scale (range 0-100). It is obtained using a Med-05-100 VAS Pain Scale ruler (Schlenker Enterprises Ltd, Lombard, USA) with 0-100 mm slider. It is measured based on the pain experienced on the IV cannulated hand for blood transfusion. Higher VAS score indicates greater intensity or degree of pain whilst lower VAS score indicates lesser pain intensity.
Skin Conductance Algesimeter Index
Time frame: The measurements will be made at 1 minute after IV cannulation which will be inserted following EMLA (with our without microneedle) application
The skin conductance peaks per second, measured in microSiemens per second (μS/s), is obtained using PainMonitor™ (Med-Storm Innovation AS, Oslo, Norway) device on the hypothenar eminence of the opposite hand not receiving blood transfusion. Higher skin conductance algesimeter index indicates greater pain intensity and lower values indicate lesser pain intensity.
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 2 Sep 2022.
- Background: PubMed 30551375Waghule T, Singhvi G, Dubey SK, Pandey MM, Gupta G, Singh M, Dua K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomed Pharmacother. 2019 Jan;109:1249-1258. doi: 10.1016/j.biopha.2018.10.078. Epub 2018 Nov 9.
- Background: PubMed 33121041Tucak A, Sirbubalo M, Hindija L, Rahic O, Hadziabdic J, Muhamedagic K, Cekic A, Vranic E. Microneedles: Characteristics, Materials, Production Methods and Commercial Development. Micromachines (Basel). 2020 Oct 27;11(11):961. doi: 10.3390/mi11110961.
- Background: PubMed 24308565Mooney K, McElnay JC, Donnelly RF. Children's views on microneedle use as an alternative to blood sampling for patient monitoring. Int J Pharm Pract. 2014 Oct;22(5):335-44. doi: 10.1111/ijpp.12081. Epub 2013 Dec 6.
- Background: PubMed 31731656Pires LR, Vinayakumar KB, Turos M, Miguel V, Gaspar J. A Perspective on Microneedle-Based Drug Delivery and Diagnostics in Paediatrics. J Pers Med. 2019 Nov 15;9(4):49. doi: 10.3390/jpm9040049.
- Background: PubMed 22575858Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012 Nov;64(14):1547-68. doi: 10.1016/j.addr.2012.04.005. Epub 2012 May 1.
- Background: PubMed 1603740de Waard-van der Spek FB, van den Berg GM, Oranje AP. EMLA cream: an improved local anesthetic. Review of current literature. Pediatr Dermatol. 1992 Jun;9(2):126-31. doi: 10.1111/j.1525-1470.1992.tb01228.x. No abstract available.
- Background: PubMed 16162086Houck CS, Sethna NF. Transdermal analgesia with local anesthetics in children: review, update and future directions. Expert Rev Neurother. 2005 Sep;5(5):625-34. doi: 10.1586/14737175.5.5.625.
- Background: PubMed 30633972Duarah S, Sharma M, Wen J. Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population. Eur J Pharm Biopharm. 2019 Mar;136:48-69. doi: 10.1016/j.ejpb.2019.01.005. Epub 2019 Jan 8.
- Background: PubMed 26131647Ita K. Transdermal Delivery of Drugs with Microneedles-Potential and Challenges. Pharmaceutics. 2015 Jun 29;7(3):90-105. doi: 10.3390/pharmaceutics7030090.
- Background: PubMed 31807980Ali R, Mehta P, Arshad MS, Kucuk I, Chang MW, Ahmad Z. Transdermal Microneedles-A Materials Perspective. AAPS PharmSciTech. 2019 Dec 5;21(1):12. doi: 10.1208/s12249-019-1560-3.
- Background: PubMed 25940042Caffarel-Salvador E, Tuan-Mahmood TM, McElnay JC, McCarthy HO, Mooney K, Woolfson AD, Donnelly RF. Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations. Int J Pharm. 2015 Jul 15;489(1-2):158-69. doi: 10.1016/j.ijpharm.2015.04.076. Epub 2015 May 1.
- Background: PubMed 17597381Kolli CS, Banga AK. Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm Res. 2008 Jan;25(1):104-13. doi: 10.1007/s11095-007-9350-0. Epub 2007 Jun 28.
- Individual participant dataSharing planned: Yes. Anonymized Individual Participant Data (IPD) with information such as date of birth, hospital registration number and others that may lead to patient identification removed will be shared via Harvard Dataverse Repository after the end of trial and data collection.
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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.
FOOK-CHOE CHEAH, MD, MRCPCH, PhD principal investigator
HOSPITAL CANSELOR TUANKU MUHRIZ, UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTER
AZRUL A HAMZAN, BSc, PhD principal investigator
INSTITUTE OF MICROENGINEERING AND ELECTRONICS (IMEN), UKM
CHANG FU DEE, BSc, PhD principal investigator
INSTITUTE OF MICROENGINEERING AND ELECTRONICS (IMEN), UKM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Microneedle, 1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time) and 1 Finger Tip Unit (FTU) EMLA (15-minute application time) in people with Thalassemia in Children, run by Universiti Kebangsaan Malaysia Medical Centre at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 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 2 Sep 2022. 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 Malaysia. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Visual Analogue Score (VAS) (time frame: The measurements will be made at 1 minute after IV cannulation which will be inserted following EMLA (with or without microneedle) application). The study lists 2 primary outcomes in all. 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 NCT05078463, which also lists 18 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 2 Sep 2022.