Study to evaluate the efficacy and safety of a local anesthetic used in flat foot or inguinal hernia interventions at two different concentrations (1% and 2%) given to two distinct groups of patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sintetica S.A.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

11 Mar 2019 → 17 Oct 2025

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518179-76-00

EudraCT number

2018-000656-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Dose response, Efficacy

The primary objective of the study is the assessment of the efficacy of chloroprocaine
1% and 2%, administered by perineural, ultrasound-guided, injection in pediatric
population for a successful peripheral nerve block (same volume ml/Kg) in terms of
proportions of subjects not requiring rescue anesthesia during surgery.

Secondary objectives 1

1. Efficacy: Time necessary for the onset of sensory block starting from the end of the injection in case of inguinal and calcaneal hernia repair stop; Time to regression of the motor block using a standard Bromage scale in case of calcaneo stop; Intensity of pain; Time required to reach the eligibility requirements for Discharge; if rescue anaesthesia (fentanyl) was required during both surgical procedures performed; time and dosage of rescue anaesthesia (fentanyl) required during surgery, in addition to IMPs injection. Safety: the general tolerability and safety of the study drug, assessed through summaries of adverse events;pain at injection site, neurological symptoms (such as: convulsions) and cardiac symptoms (such as bradycardia and heart failure etc.) evaluated during surgery after IMP injection.

Conditions and MedDRA coding

Calcagno stop and inguinal hernia repair

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000639-PIP03-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Male and femalepaediatric patients aged 28 days from birth to <18 years scheduled for: - 'calcaneo stop' surgery (6 to <18 years; children and adolescents)planned for sciatic nerve block short-lasting anaesthesia, - inguinal hernia repair (28 days from birth to 6 years; newborn infants, infantstoddlers and children)planned for ilioinguinal/iliohypogastric block short-lasting anaesthesia; 2. Normally active and otherwise judged to be in good health on the basis of medical history, physical examination, with normal lean body mass (BMI18,5 – 24,9 Kg/m2 inclusive) or normal body development (normal weight and height according to local paediatric Height and Weight Chart); 3. ASA I and ASA II patients 4. Written informed consent provided by parents/tutor, willing and able to understand the purpose of the study, including possible risks and side effects, and willing and able to comply, on their behalf and of the minor, with the study requirements. 5. Willing and able to give additional written informed consent by itself, in case of children and adolescents, in addition to parents/tutor. 6. Willing and able, in case of children and adolescents, to comply with the study requirements on their behalf.

Exclusion criteria 1

1. 1. ASA > II patients 2. Preexistent infection at injection site; 3. Use of opioids, antidepressants, anticonvulsant, sulfonamide, vasopressors, ergottype oxytocic drug and mixtures of local anaesthetics, antiarrhythmic drug class III, such as amiodarone, strong inhibitors of CYP1A2, such as fluvoxamine and enoxacin; 4. Use of medication(s) known to interfere with the extent of regional blocks for 2 weeks before the start of the study; 5. History of drug or alcohol abuse; 6. Sensitivity among the study medication active ingredient, the members of the PABA esters group and amides-type local anesthetic group; 7. Clinical history of allergy, hypersensitivity or intolerance to the study medication or other medications used during surgery; 8. Pregnancy and lactation: positive pregnancy test at screening (if applicable), pregnant or lactating (the pregnancy test will be performed to all fertile subset) 9. Participation in any other clinical study within the 3 months prior to the screening 10. Patient’s weight > 72 Kg.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint of the study will be represented by the overall proportion of patients, in each of the two dosage level groups, not requiring rescue anesthesia during surgery.

Secondary endpoints 11

1. 1 Proportion of patients, in both of the two dosage level groups, not requiring rescue anaesthesia (fentanyl) during the two surgical procedures separately;
2. 2 Time to onset of sensory block, defined as the time period from completion of the injection (time 0 min) to the achievement of complete sensory block, assessed by pinprick test associated with heart rate measurement, and evaluated for both surgeries;
3. 3 Time to regression of motor block evaluated in ‘calcaneo stop’ surgery only and assessed by a grade I of the standard Bromage scale (i.e. free movement of legs and feet). This evaluation will be performed immediately after the awakening and it will be repeated 30 minutes, 1 hour, 2 hours and 3 hours after the first evaluation, as well as during the visit for discharge
4. 4 (a) Pain intensity evaluated five times in the first 3 hours after patient’s awakening and during the home discharge visit (V2). Post-surgery assessment will be performed immediately after the awakening and it will be repeated 30 minutes, 1 hour, 2 hours and 3 hours after the first evaluation.
5. 4 (b)The technique and appropriate scale for pain measurement are age-dependent therefore, different tools will have to be used for the evaluation: -COMFORT scale for patients <2 months of age; -FLACC scale for patients aged = 2 months = 6 years; -Wong-Baker scale for patients over 6 years of age;
6. 5 Time to eligibility for home discharge, defined as: “the time elapsed from completion of surgery to the time when criteria for discharge are met, regardless if the patient will be discharged from the hospital at a later time, according to the hospital procedures”. The criteria for discharge will be defined according with the Pediatric Post Anesthesia Discharge Scoring System (Ped-PADSS)
7. 6 Time from completion of IMP injection to rescue anaesthesia, whenever required 7 Posology of rescue anaesthesia, whenever required 8 Proportion of patients requiring additional analgesia (Tramadol) after surgery, other than paracetamol i.v. administered after the surgery as per hospital’s standard procedures
8. 9 Type and posology of rescue analgesia required during the 7 days after surgery for each one of the two surgical procedures Safety: 10 Patient general recovery, evaluated by the Investigator through the evaluation questionnaire on the day of the intervention
9. 11 Patient general recovery, evaluated by the Investigator or his deputy through the F.U 24 H evaluation questionnaire on the day after intervention 12 Patient general recovery, evaluated by the Investigator or his deputy through the F.U 7-day evaluation questionnaire 7 days after intervention
10. 13 Overall proportion and 95% CI of patients with prolonged post-operative temporary loss of sensation and/or motor activity 14 Vital signs at rest (heart rate, systolic/diastolic blood pressure, respiratory rate, body temperature)
11. 15 Proportion of patients with AE, in each of the two dosage level groups and in the two surgical procedures 16 Summaries of adverse events (AEs), including pain at injection site, neurological symptoms(such as: convulsion) and cardiac symptoms (such as bradycardia and heart failure etc.) evaluated, during surgery, after IMP injection

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sintetica S.A.

Sponsor organisation

Sintetica S.A.

Address

Via Penate 5

City

Mendrisio

Postcode

6850

Country

Switzerland

Scientific contact point

Organisation

Sintetica S.A.

Contact name

Anna Guaita

Public contact point

Organisation

Sintetica S.A.

Contact name

Anna Guaita

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications