Efficacy of Transdermal Microneedle Patch for Topical Anesthesia Enhancement in Paediatric Thalassemia Patients
Condition: Thalassemia in Children
MeSH terms: Thalassemia
Study type: Interventional
Phase: Phase 2

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. 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.
    

Intervention name(s): 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
Intervention type(s): Device; Drug; Drug; Drug; Device
Intervention description(s): 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 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 applied for 15 minutes on the dorsal surface of the IV cannulated hand; 0.5 Finger Tip Unit (FTU) EMLA applied for 30 minutes on the dorsal surface of the IV cannulated hand for blood transfusion; 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.
Other intervention name(s): 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
Intervention MeSH terms: Lidocaine, Prilocaine Drug Combination; Terephthalic acid
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Microneedle; Maltose Microneedle; Thalassemia in Children; Paediatric Thalassemia; Transdermal microneedle patch; EMLA; Intravenous cannulation; Blood transfusion; Intravenous line insertion