Efficacy of Transdermal Microneedle Patch for Topical Anesthesia Enhancement in Paediatric Thalassemia Patients

NCT ID: NCT05078463

Last Updated: 2022-09-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-15

Study Completion Date

2022-08-11

Brief Summary

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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

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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

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Thalassemia in Children

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers
A Sham PVA-PET Patch that has the same size and structure as the maltose microneedle will be used. The participants, care providers and outcome assessors will not be able to distinguish between the maltose and sham patch due to their similar size and structure. One of the study investigators (Ooi Kai Shen) will not be masked since the person will be instituting the interventions. However, the study investigator (Ooi Kai Shen) is not one of the outcome assessors or care providers for the study participants.

Study Groups

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Intervention A: Microneedle with 1 Finger Tip Unit (FTU) EMLA for 30 minutes

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.

Group Type EXPERIMENTAL

Microneedle

Intervention Type DEVICE

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)

Intervention Type DRUG

1 Finger Tip Units (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion

Intervention B: Microneedle with 0.5 Finger Tip Unit (FTU) EMLA for 30 minutes

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.

Group Type EXPERIMENTAL

Microneedle

Intervention Type DEVICE

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.

0.5 Finger Tip Unit (FTU) EMLA (30-minute application time)

Intervention Type DRUG

0.5 Finger Tip Unit (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion

Intervention C: Microneedle with 1 Finger Tip Units (FTUs) EMLA for 15 minutes

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.

Group Type EXPERIMENTAL

Microneedle

Intervention Type DEVICE

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 (15-minute application time)

Intervention Type DRUG

1 Finger Tip Unit (FTU) EMLA applied for 15 minutes on the dorsal surface of the IV cannulated hand

Intervention D: 1 Finger Tip Unit (FTUs) EMLA only and PVA-containing PET Sham Patch

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.

Group Type SHAM_COMPARATOR

1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time)

Intervention Type DRUG

1 Finger Tip Units (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion

Sham Patch

Intervention Type DEVICE

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.

Interventions

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Microneedle

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.

Intervention Type DEVICE

1 Finger Tip Unit (FTU) EMLA Cream (30-minute application time)

1 Finger Tip Units (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion

Intervention Type DRUG

1 Finger Tip Unit (FTU) EMLA (15-minute application time)

1 Finger Tip Unit (FTU) EMLA applied for 15 minutes on the dorsal surface of the IV cannulated hand

Intervention Type DRUG

0.5 Finger Tip Unit (FTU) EMLA (30-minute application time)

0.5 Finger Tip Unit (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion

Intervention Type DRUG

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.

Intervention Type DEVICE

Other Intervention Names

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Maltose Microneedle Array Patch Maltose Microneedle Patch EMLA topical cream EMLA topical cream EMLA topical cream Polyvinyl Alcohol (PVA)-containing Polyethylene Terephthalate (PET) Sham Patch

Eligibility Criteria

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Inclusion Criteria

1. Patients aged at least 6 to 17 years old
2. Patients requiring venous cannulation for blood transfusion

Exclusion Criteria

1. Patients with a previous history of sensitization or allergy to EMLA cream
2. 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)
3. Patients receiving other forms of analgesic agents within 24 hours prior to the cannulation procedures
4. Patients with generalized skin disorders / rash
5. Patients who are agitated or aggressive
Minimum Eligible Age

6 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institue of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia

UNKNOWN

Sponsor Role collaborator

Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI)

UNKNOWN

Sponsor Role collaborator

Universiti Kebangsaan Malaysia Medical Centre

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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FOOK-CHOE CHEAH, MD, MRCPCH, PhD

Role: PRINCIPAL_INVESTIGATOR

HOSPITAL CANSELOR TUANKU MUHRIZ, UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTER

AZRUL A HAMZAN, BSc, PhD

Role: PRINCIPAL_INVESTIGATOR

INSTITUTE OF MICROENGINEERING AND ELECTRONICS (IMEN), UKM

CHANG FU DEE, BSc, PhD

Role: PRINCIPAL_INVESTIGATOR

INSTITUTE OF MICROENGINEERING AND ELECTRONICS (IMEN), UKM

XIN YUN CHUA, BSc

Role: PRINCIPAL_INVESTIGATOR

HOSPITAL CANSELOR TUANKU MUHRIZ, UKM (UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTRE)

Locations

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Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia (Ukm Medical Centre)

Kuala Lumpur, Kuala Lumpur, Malaysia

Site Status

Countries

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Malaysia

References

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Reference Type BACKGROUND
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Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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PRGS/2/2020/TK05/UKM/01/1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

UKM PPI/111/8/JEP-2021-578

Identifier Type: -

Identifier Source: org_study_id

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