Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the daily pain level scores for patients taking opioids alone for pain relief, compared with those treated by multimodal analgesia with three medications: pregabalin, naproxen, and acetaminophen, with the ability to switch over to opioid medications if needed. In addition to pain level scores, this study will compare opioid use (length of time and doses taken), quality of life, admissions to hospital, feeding tube requirements, weight loss, and treatment interruptions between these two analgesic regimens.

Detailed Description
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A significant proportion of patients undergoing radiotherapy alone or chemotherapy and radiotherapy together for their head and neck cancer experience mucositis, which is severe pain in the mouth and throat caused by radiation treatment. Patients often enter a cycle of pain, difficulty swallowing, malnourishment, and reduced quality of life. This may translate into decreased oral intake requiring a feeding tube, and radiation or chemotherapy treatment breaks, which reduce the chance of tumour control and cure. Currently, opioid therapy is the cornerstone of head and neck cancer pain management. Although effective for pain relief, opioids can have side effects. As an alternative to opioid treatments, multimodal analgesia is a treatment using medications from different classes with different mechanisms of action. Examples of analgesic medications used for multimodal analgesia include medications similar to acetaminophen or ibuprofen, and others. The primary purpose of this study is to compare pain level scores of patients taking opioids versus patients taking multimodal analgesia.

Official Title
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Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer: A Randomized Clinical Trial

Conditions
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Head and Neck Cancer, Radiation-Induced Mucositis

Intervention / Treatment
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* Drug: Opioids
* Drug: PAiN - multimodal analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Willing to provide consent Histologically confirmed mucosal head and neck malignancy Undergoing chemoradiotherapy or radiotherapy alone with a planned total radiation dose of 50 Gray (Gy) or greater Eastern Co-operative Oncology Group (ECOG) performance status 0-2 Life expectancy > 6 months Onset of 4/10 pain on the 11-Numeric Rating Scale that is localized to the mucosa of the mouth or throat, before or during radiation treatment, that is not caused by a current oral candidiasis infection. Ability to take pills, either by mouth or crushed via NasoGastric (NG) tube or Gastrostomy tube (G-tube) Ability to complete the study questionnaires and pain diary Ability to sign consent without requirement for a substitute decision maker Exclusion Criteria: Skin and salivary gland malignancies High daily opioid use at time of enrollment (defined as 30 mg oral morphine equivalent dose or higher) Concurrent second active malignancy Pregnant or lactating women Psychological disorder requiring pharmacologic treatment Regular systemic steroid use Regular anticonvulsant or antidepressant use Renal Impairment (defined as creatinine clearance < 60 mL/min) Liver Dysfunction (defined as total bilirubin > 34.2 µmol/L) Documented true allergy to acetaminophen, NSAIDs, pregabalin or opioids History of upper gastrointestinal bleed Known bleeding disorder History of or current substance use disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Opioid Analgesia<br>Opioids will be prescribed as per institutional standards. Examples of opioids are morphine and hydromorphone. | Drug: Opioids<br>* Opioids will be prescribed as per institutional standards.<br>|
| Experimental: Multimodal Analgesia<br>Pregabalin (50 mg to 300 mg, oral, twice daily), acetaminophen (1000 mg, oral, 3 times per day), naproxen 250 mg to 500 mg, oral, twice daily), and pantoprazole magnesium (40 mg, oral, daily) | Drug: PAiN - multimodal analgesia<br>* PAiN: Pregabalin, Acetaminophen, Naproxen, pantoprazole magnesium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Pain Rating measured on the 11 Numeric Rating Scale | Average pain rating during the last 7 days of radiation therapy, as reported by the patient on the 11-Numeric Rating Scale (11-NRS). On the 11-NRS, zero (0) is no pain, and ten (10) is the worst possible pain. | Approximately 2 years and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Weekly Opioid Use | The average weekly total opioid dose in oral morphine equivalent dosing from randomization to 6 weeks after completion of radiation treatment. | Approximately 2 years and 4 months | 
| Duration of Opioid Requirement | The time from the start of opioid treatment after randomization to the time of stopping opioid analgesia, in days. | Approximately 2 years and 6 months | 
| Average Daily 11-Numeric Rating Scale for Pain | Average pain rating from the time of randomization until 6 weeks after completion of radiation treatment, as reported by the patient on the 11-Numeric Rating Scale (11-NRS). On the 11-NRS, zero (0) is no pain, and ten (10) is the worst possible pain. | Approximately 2 years and 4 months | 
| Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Quality of life, as reported by the patient, will be assessed using the EORTC QLQ-C30 validated questionnaire. Responses regarding function and symptoms are on a scale of 1 (not at all) to 4 (very much). Also included are questions about overall health and quality of life. Responses are on a scale of 1 (very poor) to 7 (excellent). | Approximately 24 months, 27 months, and 30 months | 
| Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Head & Neck 43 (EORTC QLQ-HN 43) | Quality of life, as reported by the patient, will be assessed using the EORTC QLQ-HN 43 validated questionnaire. Responses regarding symptoms or problems are on a scale of 1 (not at all) to 4 (very much). This questionnaire is specifically for patients with head and neck cancer. | Approximately 24 months, 27 months, and 30 months | 
| Average Weekly Opioids Dispensed | The average weekly total opioid dose dispensed by the pharmacy in oral morphine equivalent dosing from randomization to 6 weeks after completion of radiation treatment. | Approximately 2 years and 4 months | 
| Hospital Admissions | Hospital admissions for febrile neutropenia, serious infection requiring intravenous antibiotics, gastrointestinal bleeding, myocardial infarction, stroke, and acute kidney injury. | Approximately 27 months and 30 months | 
| Time to Feeding Tube Insertion | The time to feeding tube insertion (e.g. gastrostomy-tube or nasogastric-tube) after randomization, in days. | Approximately 2 years and 3 months | 
| Weight Loss | Weight loss from randomization to the end of radiation treatment. | Approximately 2 years and 3 months | 
| Rates of Common Terminology Criteria for Adverse Events Toxicities | Rates of pre-specified Common Terminology Criteria for Adverse Events (CTCAE) toxicities. | Approximately 2 years and 6 months | 
| Treatment Interruptions | Number of participants with radiation of chemotherapy treatment interruptions. | Approximately 2 years and 6 months | 
| Death | Number of participants who die during or within 3 months after completion of radiation treatment. | Approximately 2 years and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Analgesia