Intrathecal baclofen pump versus selective dorsal rhizotomy for non-ambulatory children with cerebral palsy

The primary objective is to compare health-related quality of life, safety profile, cost effectiveness, and cost utility at one year following selective dorsal rhizotomy (SDR) and intrathecal baclofen (ITB) therapy in non-ambulatory children with spastic cerebral palsy. This comparison addresses a clinically important gap in understanding the relative benefits and risks of two established neurosurgical interventions for managing severe spasticity in this population, informing treatment selection based on functional outcomes, economic considerations, and patient wellbeing.

The secondary objectives encompass a comprehensive evaluation over an eight-year period comparing the following parameters between SDR and ITB:

• Quality of life, safety, cost effectiveness, and cost utility
• Spasticity severity and passive range of motion
• Trunk control and fine motor function
• Communication abilities and orobulbar function (swallowing)
• Lower urinary tract symptoms and sleep quality
• Utilization of antispasmodic drugs and analgesics
• Parental distress levels
• Attainment of individualized treatment goals and patient satisfaction

These secondary outcomes provide longitudinal data on functional domains, symptom burden, medication requirements, and psychosocial impact, enabling a multidimensional assessment of treatment efficacy and tolerability in non-ambulatory children with spastic cerebral palsy.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population comprises **male and female pediatric patients** aged **4 to less than 18 years** diagnosed with **spastic cerebral palsy**. Participants are classified as **non-ambulatory**, corresponding to **Gross Motor Function Classification System (GMFCS) grade 4 or 5**. The trial population was selected based on inadequate control of **spasticity** with conservative therapy and/or oral **baclofen**, or the presence of intolerable side effects from such treatments. This study involves a **vulnerable population**. Key inclusion criteria specify that participants must have provided voluntary written **informed consent** through their legally authorized representative, with age-appropriate **informed assent** obtained from the child. Participants are permitted to continue or modify their usual medication during the study, with **concomitant medication** being monitored throughout to assess potential reduction over time. Cross-over neurosurgical procedures are not permitted during the first year of the trial.

This clinical trial is designed as a comparative study evaluating two established treatment modalities for managing spasticity in non-ambulatory children with **cerebral palsy**. The trial compares **intrathecal baclofen** pump therapy with **selective dorsal rhizotomy** in pediatric participants classified as **Gross Motor Function Classification System** (GMFCS) grade 4 or 5. The study is categorized as a **low-intervention clinical trial** because the investigational medicinal product, intrathecal baclofen, is used in full accordance with the terms of its marketing authorization, and both interventions represent established standard-of-care options. The trial does not introduce risks or burdens beyond those encountered in normal clinical practice.

The investigational medicinal products utilized in this trial include **baclofen** formulations administered via **intrathecal use**. Three authorized products are employed: Lioresal Intrathecal Infusion 10mg/5ml, Lioresal Intrathecal Infusion 10mg/20ml, and Baclofen Aguettant 2 mg/mL solution for infusion. All formulations are solutions for injection or infusion containing baclofen as the active substance of chemical origin. The maximum daily dose is 2000 micrograms, with a maximum total dose of 2000 micrograms. The maximum treatment period ranges from 702 to 704 days, depending on the specific product formulation used.

Participant eligibility requires males and females aged 4 years to less than 18 years with spastic cerebral palsy and GMFCS classification of grade 4 or 5. Included participants must have spasticity insufficiently controlled with conservative therapy and/or oral baclofen, or experience intolerable side effects from such treatments. Voluntary written informed consent from the participant or their legally authorized representative is mandatory prior to any screening procedures, and informed assent must be obtained from the child in a manner appropriate for their age and understanding. Participants are permitted to continue or change their usual medication during the study, with concomitant medication registered throughout to evaluate potential dose reductions over time. Cross-over neurosurgical procedures are not allowed during the first year to avoid influencing the impact of the evaluated techniques.

The primary endpoint of the trial is the change in **CP-CHILD** caregiver version score, measured in absolute value, comparing the first year postoperatively to the immediate preoperative period, with a non-inferiority margin set at a clinically meaningful difference of 5 out of 100. Key secondary endpoints include assessment of **adverse events**, **cost-effectiveness**, and **cost-utility**. Additional secondary endpoints encompass evaluation of spasticity, range of motion, trunk control, communication, orobulbar function, sleep quality, urinary symptoms, spinal and hip deformities, medication use, quality of life, treatment goals, parental distress, patient satisfaction, healthcare costs, and complications.

The estimated recruitment start date for the trial is January 1, 2026, with an estimated end date of April 30, 2039, indicating an extended trial duration to accommodate long-term follow-up and comprehensive data collection. The duration of participant involvement is primarily focused on the first postoperative year for primary outcome assessment, though extended follow-up may be conducted to evaluate long-term outcomes and safety. Conditions that may lead to early termination from the study include withdrawal of consent, occurrence of serious adverse events requiring discontinuation, need for cross-over neurosurgical intervention, loss to follow-up, or investigator decision based on safety concerns or protocol violations. The trial procedures are designed to align with routine clinical practice, minimizing additional burden on participants while systematically comparing the health-related quality of life, safety profile, and economic impact of the two neurosurgical interventions.

The experimental treatment consists of **baclofen** administered via **intrathecal** route. Three authorized medicinal products containing baclofen are utilized in this clinical trial. **Lioresal® Intrathecal Infusion 10mg/5ml** is presented as a **solution for injection/infusion** and is manufactured by NOVARTIS PHARMACEUTICALS UK LIMITED. Lioresal® Intrathecal Infusion 10mg/20ml, also formulated as a solution for injection/infusion, is provided by the same manufacturer. **Baclofen Aguettant 2 mg/mL solution for infusion** is manufactured by LABORATOIRE AGUETTANT and is presented as a **solution for infusion**. All three products contain baclofen as the **active substance** of chemical origin.

The **maximum daily dose** for baclofen administration is established at **2000 micrograms** across all three formulations. The maximum total dose amount is similarly set at 2000 micrograms. The **maximum treatment period** is defined as 704 days for both Lioresal® formulations and 702 days for Baclofen Aguettant formulation. All medicinal products are administered exclusively via intrathecal use, ensuring direct delivery of the active substance to the **intrathecal space**. The **pharmaceutical form** of these products is designed specifically for infusion or injection/infusion purposes, facilitating continuous or intermittent administration through an intrathecal delivery system.

The dosing regimen and administration schedule are designed to maintain therapeutic baclofen concentrations within the intrathecal space throughout the treatment period. The use of pump-based delivery systems enables precise control of drug administration and allows for individualized **dose titration** based on clinical response and tolerability. Participant compliance monitoring is facilitated through the use of programmable intrathecal pumps, which provide accurate records of drug delivery and enable healthcare professionals to verify adherence to the prescribed dosing schedule.

Efficacy will be assessed using the primary endpoint of change in the CP-CHILD caregiver version score, measured in absolute value, comparing the first year postoperatively versus immediately preoperatively. The non-inferiority margin is defined as a clinically meaningful difference of 5 out of 100 points. Key secondary endpoints include the evaluation of adverse events, cost-effectiveness, and cost-utility. Additional secondary endpoints encompass multiple parameters including spasticity, range of motion, trunk control, communication, orobulbar function, sleep quality, urinary symptoms, spinal and hip deformities, medication use, quality of life, treatment goals, parental distress, patient satisfaction, healthcare costs, and complications. The assessment will compare outcomes between intrathecal baclofen pump therapy and selective dorsal rhizotomy in non-ambulatory children with spastic cerebral palsy. The primary objective is to compare health-related quality of life, safety profile, cost effectiveness, and cost utility one year after each intervention.