Conventional Medical Management, Intrathecal Drug Delivery, Refractory Cancer Pain
Conditions
Keywords
Intrathecal pumps, Intrathecal drug delivery, Refractory cancer pain, Health-related quality of life, Neuromodulation
Brief summary
Approximately 66% of patients with advanced cancer experience pain, which is often inadequately controlled and associated with a decline in health-related quality of life (HRQoL). Conventional pharmacologic management, ranging from simple analgesics to strong opioids, is frequently limited by insufficient efficacy and systemic side effects. Intrathecal drug delivery (IDD) offers targeted, continuous medication infusion directly into the intrathecal space, allowing lower systemic doses and potentially reducing side effects while maintaining effective analgesia. The CAREGIVER study is a randomized, controlled trial designed to evaluate whether patients with severe refractory cancer pain receiving IDD experience a difference in HRQoL compared to those receiving conventional medical management (CMM) with oral pain medications.
Interventions
PROCEDUREIntrathecal Drug Delivery
Patients assigned to the IDD-group (intervention group) will undergo implantation of an IDD pump (Synchromed™, Medtronic). The device will be placed subcutaneously in the abdominal region and connected to a catheter delivering pain medication directly into the intrathecal space surrounding the spinal cord. At the time of implantation, the pump will be filled with medication, such as morphine, local anesthetics, or a combination thereof, and an initial daily dose will be selected. In the days following surgery, dose titration will be performed to establish the optimal balance between pain relief and tolerability. Following implantation, the most common postoperative procedure is the drug refill. This involves aseptic access to the pump reservoir, removal of any residual volume, and replenishment with a fresh dose of medication. Refill intervals will depend on the patient's daily dosage, ranging from monthly to once every 2-3 months.
Participants randomized to the CMM-group will receive standard care.
Sponsors
Universitair Ziekenhuis Brussel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (≥18 years) with severe cancer refractory pain (all types of cancer), who have been receiving treatment with oral/systemic opioids for at least 4 weeks, and are expected to remain on opioids for the entire duration of the study. More than one opioid rotation has to be done before defining pain refractoriness. * Intrathecal therapy is recommended because of inefficacy or intolerance to strong systemic opioid treatment. Inefficacy is defined as mean daily visual analogue scale (VAS) pain intensity score at rest of ≥ 50 mm. Intolerance is defined as the occurrence of (S)AEs (even with dosage less than 200 mg/day of oral morphine equivalents) which prevents a further increase in the opioid dosage to obtain pain relief. * Patients suitable for IDD and with the ability to comply with the medical protocol and visits. * Survival prognosis of ≥ 6 months.
Exclusion criteria
* Patients with active, severe infection. * Patients with known brain metastases. * Patients with high risk of hemorrhaging. * Patients with respiratory depression (for use of morphine). * Patients with severe respiratory compromise; baseline oxygen SpO2 \< 90%, chronic CO2 retention. * Patients with severe cardiac disease or risk of cardiotoxicity (for use of bupivacaine). * Patients with severe liver impairment or liver failure (for use of ropivacaine). * Patients with allergies for medication or IDD hardware. * Pregnant or lactating women. * Women who plan to become pregnant within 1 month after the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health-related quality of life | At baseline and 1, 2, 4, 6, 8, 10, and 12 months post-treatment initiation | Health-related quality of life will be evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient comfort | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | Patient comfort is evaluated with the General Comfort Questionnaire (GCQ), a self-reported instrument consisting of 48 items that reflect the physical, spiritual, environmental, and social dimension. |
| Survival | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | The survival rate will be determined by recording the time from treatment initiation until death. |
| Pain intensity | At baseline and 1, 2, 4, 6, 8, 10, and 12 months post-treatment initiation | Pain intensity will be measured with the Visual Analogue Scale (ranging from 0 (no pain) to 100 (maximal pain)) in electronic format. Momentary data collection will be used to collect pain intensity scores for VAS (valid and reliable for pain experience), whereby pain intensity is measured for multiple times per day for 1 week to reveal patterns of transient or fluctuating symptoms in the environment and context of the patients' lives, without a recall bias. |
| Perceived stress | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | Perceived stress will be assessed by using the 10-item Perceived Stress Scale. |
| Anxiety | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | Patient anxiety will be provided through the State Trait Anxiety Inventory (STAI). |
| Perceived Injustice | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | Using the Injustice Experience Questionnaire (IEQ), perceived injustice related to current health status will be assessed. |
| Self-efficacy | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | The General Self-Efficacy (GSE) Scale is a 10-item self-report questionnaire used to assess perceived self-efficacy. |
| Caregiver burden | At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation | To evaluate caregiver burden, the Zarit Burden Interview (ZBI) questionnaire will be completed. This 12-item self-report instrument assesses caregiver burden and is a shortened version of the original 22-item Zarit Burden Scale. |
| Health expenditure | monthly after treatment initiation until 12 months | Expenditures related to in-hospital care will be extracted from hospital claims data. All other healthcare-related costs will be gathered through telephone interviews with patients, conducted each month after treatment initiation. During these calls, researchers will ask patients whether they have had any medical consultations, hospital admissions, AEs, changes in medication (such as daily morphine, MED, antidepressants,…), or incurred any additional healthcare costs. |
| Safety | Throughout the duration of the study, an average of 12 months. | Recording of (serious) adverse events. |
| Number of responders | at 1, 2, 4, 6, and 12 months post-treatment initiation | Responder status will be determined based on pain scores, adverse events, and medication dose changes. Responders are defined as patients achieving a clinically meaningful reduction in pain intensity (≥30% from baseline) without intolerable adverse effects. |
Countries
Belgium
Contacts
CONTACTMaarten Moens, MD PhD MBA
CONTACTLisa Goudman, MSC, PhD
Outcome results
None listed