Intrathecal Ziconotide and Combination Therapy versus Comprehensive Medical Management for Severe Refractory Cancer Pain: A Randomized Controlled Trial

The primary objective of this study is to evaluate the impact of intrathecal drug delivery systems compared to comprehensive medical management on health-related quality of life in patients with severe refractory cancer pain. The secondary objectives include the assessment of:

• Pain intensity and comfort;
• Survival;
• Psychological factors including anxiety, perceived stress, perceived injustice, and self-efficacy;
• The burden on caregivers;
• Health expenditure;
• Safety.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients, aged 18 to 65 years, including both males and females, diagnosed with severe refractory cancer pain. Participants must have received opioid treatment for a minimum of four weeks and are expected to continue this therapy throughout the study period. Refractoriness is defined by the completion of more than one opioid rotation. The population includes individuals for whom intrathecal therapy is indicated due to the inefficacy or intolerance of systemic treatments. Inefficacy is characterized by a mean daily visual analogue scale pain intensity score of 50 mm or greater at rest, while intolerance involves the occurrence of adverse events that limit dose escalation. Eligible subjects must be suitable for intrathecal drug delivery, possess a survival prognosis of at least three months, and demonstrate the ability to comply with the clinical protocol. The primary objective is to evaluate health-related quality of life.

This randomized controlled trial evaluates the efficacy of intrathecal drug delivery systems compared to comprehensive medical management in patients with severe refractory cancer pain. The study methodology involves comparing the use of an intrathecal pump delivering substances such as ziconotide, morphine hydrochloride, bupivacaine hydrochloride, or ropivacaine hydrochloride against standard systemic treatments. The primary objective is the assessment of health-related quality of life using the EORTC QLQ-C30 questionnaire. Secondary endpoints include pain intensity measured via the visual analogue scale, patient comfort, survival rates, perceived stress, anxiety, and caregiver burden. The research protocol includes a screening phase to identify adult patients who have received opioid therapy for at least 4 weeks and meet specific criteria for pain refractoriness or intolerance. Participants will undergo various follow-up assessments to monitor safety, adverse events, and healthcare-related costs. The trial is expected to conclude by October 2029.

The experimental intervention involves the use of ziconotide, provided as a solution for infusion at a concentration of 25 micrograms/ml. The administered dose is 21.60 µg via the intrathecal route.

Ropivacaine hydrochloride is administered as a solution for injection. The dosage is 15 mg delivered via the intrathecal route.

Morphine hydrochloride is utilized in two different pharmaceutical forms. One formulation consists of a 10 mg/ml solution for injection, while the other is a 40 mg/ml solution for injection. Both formulations are administered at a dose of 1500 µg via the intrathecal route.

Bupivacaine hydrochloride is administered as a 0.5% solution for injection. The dose is 15 mg provided via the intrathecal route.

The primary efficacy endpoint is the evaluation of health-related quality of life (HRQoL) using the EORTC QLQ-C30 questionnaire. Secondary efficacy parameters include the assessment of patient comfort via the General Comfort Questionnaire (GCQ), which utilizes a 48-item self-report instrument covering physical, spiritual, environmental, and social dimensions. Pain intensity is measured using a Visual Analogue Scale (VAS) ranging from 0 to 100 in an electronic format. Perceived stress is quantified through the 10-item Perceived Stress Scale (PSS), while patient anxiety is assessed using the State Trait Anxiety Inventory (STAI). Additional secondary endpoints include the assessment of perceived injustice related to health status via the Injustice Experience Questionnaire (IEQ), perceived self-efficacy using the General Self-Efficacy Scale (GSE), and caregiver burden measured by the Zarit Burden Interview (ZBI). The survival rate is determined by recording the time from treatment initiation until death. Economic evaluations involve the extraction of in-hospital care expenditures from hospital claims data and the collection of other healthcare-related costs through monthly telephone interviews following treatment initiation. These interviews track medical consultations, hospital admissions, adverse events (AEs), and changes in medication.