Epidural Association of Morphine and Ropivacaine for Cancer Pain Treatment

Effectiveness of Epidural Morphine and Ropivacaine Treatment for Abdominal Cancer Pain in Patients of Brazilian's Public Health System

In 2012, more than 14 million cases of cancer were diagnosed worldwide, with the forecast for 2025 exceeding 20 million. Pain is the most critical symptom that accompanies cancer. The development of disease generates the need for oncological palliative care and adequacy of the structure by Public Health Care System. In this context, this study aims to evaluate an alternative to the treatment plans provided for in the Brazilian's Public Health Care System table. The objective is to carry out a cost-effectiveness analysis of the epidural administration of morphine and ropivacaine in patients with abdominal neoplasia, and pain that is difficult to clinically control, which leads to an improvement in the quality of life, functional conditions and survival of patients, and that reduces the cost to the Brazilian's Public Health Care System. This is a randomized clinical trial. Patients will be divided into two groups: control and intervention. The control group will receive oral treatment according to the Clinical Protocol and Therapeutic Guidelines for Chronic Pain of the Brazilian's Ministry of Health: morphine, pregabalin and duloxetine. The intervention group will receive an anesthetic solution containing morphine and ropivacaine for epidural administration through a surgically implanted catheter. Pain, quality of life, functional capacity and survival will be evaluated using the following instruments: Visual Analogue Scale; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire "Core" 30; Karnofsky Performance Scale; Eastern Cooperative Oncology Group Scale; Palliative Performance Scale; and Palliative Prognosis Index. It is expected that, at the end of the study, the intervention group will represent a significant savings for the Public Health Care System, due to the decrease in the number of hospitalizations/day and the possible complications due to the lack of effectiveness of the oral treatment. It is expected that the results found will produce scientific support to disseminate the proposed treatment plan for Brazilian's Public Health Care System patients in palliative care.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Palliative Care; Opioid Use; Cancer Pain; Cost Analysis; Epidural Route; Morphine-ropivacaine Association; Rational Use of Medication
• Intervention / Treatment: Drug: Control Group (Oral morphine); Device: Interventional Group (Epidural morphine)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Larissa Helena LT Pacheco, PhD; Phone Number: +55 (35) 988013379; Email: larissa.torres@unifal-mg.edu.br

Study Locations

• Brazil
  • Minas Gerais
    • Alfenas, Minas Gerais, Brazil, 37137001
      • Recruiting
      • Larissa Helena Lobo Torres Pacheco
      • Contact: Larissa Helena LT Pacheco, PhD; Phone Number: +55 (35) 988013379; Email: larissa.torres@unifal-mg.edu.br
      • Principal Investigator: Carlos Marcelo Barros, M.D.
      • Sub-Investigator: Márcia Helena MC Podestá, PhD
      • Sub-Investigator: Liliana B Vieira, PhD
      • Sub-Investigator: Carla S Ceron, PhD
      • Sub-Investigator: Vanessa B Boralli, PhD
      • Sub-Investigator: Carolina Aparecida F Almeida, MSC
      • Sub-Investigator: Rafaela F Rodrigues, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged between 18 and 75 years,
• both sexes
• diagnosed with abdominal neoplasia and with PPI < 2.0, which indicates a survival of at least 90 days
• have full cognitive conditions
• Patients must also have a caregiver with cognitive conditions.

Exclusion Criteria:

- Patients with technical incapacity to implant the catheter will be excluded, namely: patient refusal, infection at the puncture site and hemodynamic instability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group (Oral Morphine); The control group will be composed of 15 patients who will receive oral drug treatment according to the Clinical Protocol and Therapeutic Guidelines for Chronic Pain of the Brazilian Ministry of Health. The drugs included in the treatment plan are morphine (60 mg/day), pregabalin (150 mg/day) and duloxetine (60 mg/day), available free of charge to the participating patients. The treatment will be carried out orally in a home environment.	Drug: Control Group (Oral morphine); Oral administration of morphine, pregabalin or duloxetin
Experimental: Interventional Group (Epidural morphine); The intervention group will be composed of 15 patients who will undergo a surgical procedure for subcutaneous implantation of a catheter (Celsite ST304-19BBraun) that allows epidural administration of morphine and ropivacaine drugs. The treatment plan for such patients includes Patient Controlled Analgesia (PCA). Patients in this group will receive, via catheter, an anesthetic solution containing 2.0 mL of morphine (1.0 mg/mL), 3.0 mL of ropivacaine (7.5 mg/mL) and 5.0 mL of distilled water. For 24 hours after this application, if the patient continues to have pain, they may use a rescue dose of oral morphine of 10 mg.	Device: Interventional Group (Epidural morphine); Implantation of an epidural catheter for administration of morphine and ropvacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of effectiveness of epidural morphine/ropivacaine treatment	Change From Baseline in Pain Scores on the Visual Analog Scale (0 means no pain and 10 means worst pain) in patients in the control group and intervention group for up to 60 days.	Up to 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of quality of life	Change of quality of life score by the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30), which consists of a likert-type scale ranging from 1 to 4 for functions and symptoms, where 1= not at all, 2=slightly, 3= moderately, and 4 = very much. If the resulting score on the functional scale is high, this represents a healthy functional level, while a high score on the symptom scale represents a low level of symptom tolerance and treatment side effects. This scale also assesses overall health, ranging from 1 to 7, with 1=bad and 7 = very good	Up to 60 days
Assessment of functional status	Change in the patient's functional status by the Karnofsky Performance Scale (KPS), which ranges from 100% to 0%, where 100% means no evidence of disease and 0% means death	Up to 60 days
Assessment of progression of disease status	Change in disease status using the Eastern Cooperative Oncology Group (ECOG) scale, ranging from 0 to 5, where 0 = completely active and 5 =dead	Up to 60 days
Assessment of patient's clinical-functional status	Change in clinical-functional status by the Palliative Performance Scale (PPS), which ranges from 100 to 0%, where 100% = good clinical-functional status and 0%= dead	Up to 60 days
Assessment of disease prognosis	Change in survival time by the Palliative Prognosis Scale (PPI), which assesses PPS, presence of delirium, dyspnea, oral intake and edema, where each factor presents a score and at the end the scores are summed and the patient is classified into group A (Total Score < 2.0): > 6 weeks survival, group B (Total Score between 2.0 - 4.0): 3 - 6 weeks survival and group C (Total Score > 4.0): < 3 weeks survival	Up to 60 days
Cost-effectiveness analysis	For cost-effectiveness analysis, a direct cost analysis using the cost-effectiveness ratio will be used. The costs considered in this study will be the direct non-medical and direct medical costs. For direct cost analysis, the microcosting technique will be used. For economic analysis, the incremental cost-effectiveness ratio (ICER) will be used. Once a CERI is obtained, the result is evaluated by defining a cost-effectiveness threshold, which aims to identify values that society considers feasible, from an economic point of view, to be incorporated as additional costs in society's spending on health (BRASIL, 2014). Once the RCEI is obtained, the next step in a pharmacoeconomic analysis will be to perform a sensitivity analysis of the parameters involved during the research.	Up to 60 days
Quantify the plasma concentration of morphine	Patients will undergo blood draws to obtain plasma, 1:30h after taking morphine (oral or epidural) which will later be quantified for morphine by gas chromatography.	Up to 60 days
Correlating plasma morphine concentration with therapeutic effecs	The amount of morphine found in plasma (outcome 8) will be correlated with the therapeutic effects (pain levels by Visual Analog Scale)	Up to 60 days
Quantify brain-derived neurotrophic factor (BDNF)	BDNF quantification will be done in the plasma of the patients, using the BDNF enzyme-linked immunosorbent assay (ELISA) kit from sigma and adverse effects	Up to 60 days

Collaborators and Investigators

• Sponsor: Universidade Federal de Alfenas
• Collaborators: Fundação de Amparo à Pesquisa do estado de Minas Gerais
• Investigators: Study Director: Larissa LT Pacheco, PhD, Universidade Federal de Alfenas

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 2.543.790

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No