Effect of Vitamin C on Pain Reduction After an Emergency Department Visit

Pain, Acute Clinical Trial

— Vicamed  

Official title:

Does Vitamin C Provide an Analgesic Effect on Acute Musculoskeletal Injury After an Emergency Department Visit: A Double-Blind Randomized Control Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06306183
• Other study ID #: 2024-2829
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 2024
• Est. completion date: March 2028

Study information

• Verified date: March 2024
• Source: Hopital du Sacre-Coeur de Montreal
• Contact: Martin Marquis, MSc
• Phone: 514-338-2222
• Email: martin.marquis.cnmtl[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Emergency department (ED) clinicians often prescribe anti-inflammatory drugs (NSAIDs) to manage acute musculoskeletal (MSK) pain (e.g.: fracture, sprain, back pain). However, even short-term NSAIDs use can have significant gastrointestinal, cardiovascular, MSK and renal adverse effects. For this reason, some patients cannot take or tolerate NSAIDs. Recent evidence has shown that vitamin C has some analgesic and anti-inflammatory properties particularly in postoperative context and prevent specific types of chronic pain. Furthermore, vitamin C is safe and associated with very few adverse events. The primary objective of this study is to determine whether vitamin C can reduce pain intensity during a seven-day period following an ED visit for acute MSK pain. The investigators propose to compare two groups of patients, one receiving 900 mg of vitamin C to another receiving a placebo, twice a day for seven days. Both groups will consume acetaminophen slow release 650 mg two pills every eight hours regularly. Naproxen 500 mg (NSAID) will be used as a rescue medication if the patient's pain is not relieved. Participants will be ≥18 years of age, treated in ED for acute MSK pain present for less than 48 hours with pain intensity at triage of ≥ 4 on a 0-10 numeric rating scale, and discharged by an ED clinician with an NSAIDs prescription without opioids. The level of pain intensity during a seven-day period will be assessed daily using an electronic or paper diary, as well as pain relief, pain medication consumption, and adverse events. Three months after the injury, participants will also be contacted to assess the presence of chronic pain. The investigators hypothesized that vitamin C will reduce pain intensity and chronic pain development at three months. This research could provide a safe alternative to patients who are unable to take NSAIDs. It may also contribute to the reduction of the burden associated with chronic pain development.

Description:

Background and Importance: Nonsteroidal anti-inflammatory drugs (NSAIDs) have proven their efficacy and compared advantageously to opioids in treating acute musculoskeletal (MSK) pain. However, even short-term NSAIDs use for acute pain management after an emergency department (ED) discharge can have significant gastrointestinal, cardiovascular, musculoskeletal and renal adverse effects. Recent evidence has shown that vitamin C has, in addition to its antioxidant effect, some analgesic and anti-inflammatory properties. Its analgesic effect has been explored mostly in short-term postoperative context or in disease-specific chronic pain prevention, but never after acute pain from MSK injuries, which are often seen in EDs. Goal(s) / Research Aims: The primary aim is to evaluate the effectiveness of vitamin C in reducing pain intensity during a seven-day period following ED discharge for an acute MSK pain complaint. The secondary aims are to compare both treatment groups for rescue medication use, average pain relief and adverse events during a seven-day follow-up, and at three months for chronic pain incidence. Methods / Approaches / Expertise: The investigators will conduct a pragmatic five-center, double-blind randomized placebo-controlled trial (RCT) with 546 participants equally distributed in two arms; one group receiving 900 mg of vitamin C and another one receiving a placebo, twice a day for seven days. Both groups will consume acetaminophen slow release 650 mg two pills every eight hours regularly. Naproxen 500 mg will be used as a rescue medication if the patient's pain is not relieved more than one hour after acetaminophen consumption. Participants will be aged ≥18 years, treated in the emergency department for acute MSK injury present for less than 48 hours with a pain intensity at triage of ≥ 4 on a numerical rating scale (NRS) of 0-10, and scheduled for discharge by an emergency clinician with an NSAIDs prescription without opioids. Daily pain intensity during the seven-day period will be assessed via a previously tested electronic or paper diary. In addition, patients will report their daily rescue pain medication use, pain relief, and adverse events. Three months after the ED visit, participants will be contacted to evaluate chronic pain development. The investigators hypothesized that vitamin C will reduce pain intensity during a seven-day follow-up for ED discharged patients treated for acute MSK pain. This project brings together a committed, multidisciplinary research team composed of five study sites having previously collaborated on large multicenter RCT studies. All required instruments have been successfully used during an ongoing Canadian Institutes of Health Research (CIHR) grant, a non-objection letter from Health Canada has been already requested and the investigators have secured a provider for both study drugs, all this ensuring a rapid study implementation. Expected Outcomes: The investigators will provide the following outcomes for patients receiving vitamin C and placebo: pain intensity, rescue medication use, pain relief, and side effects for one-week post-discharge and chronic pain incidence at three months. Confirmation of the vitamin C analgesic effect for acute MSK pain could help patients who are unable to consume or are at risk of complications from NSAIDS. It may also contribute to the reduction of the burden associated with chronic pain development.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 546
• Est. completion date: March 2028
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years old

2. Treated in the ED for acute MSK pain present = 48 hours at triage (time to presentation for most acute MSK pain in our previous study)

3. Numerical rating scale (NRS) pain intensity at triage of = 4 on a 0-10 scale

4. Discharged with instructions to take an NSAID for pain (need determined by treating clinicians)

5. French or English-speaking

Exclusion Criteria:

1. Received an opioid prescription at ED discharge

2. Currently using vitamin C supplements

3. Active cancer

4. Currently treated for chronic pain

5. Unable to fill out a diary or unavailable for follow-up

6. Allergy, to milk (lactose in the placebo), vitamin C, acetaminophen or NSAIDs

7. Treated with cyclosporine or warfarin (interaction with vitamin C)

8. Pre-existing oxalate nephropathy, liver cirrhosis or hemochromatosis

9. Pregnant = 20 weeks.

Related Conditions & MeSH terms

• Acute Pain
• Emergencies
• Pain, Acute

Intervention

Dietary Supplement:
• Acetaminophen and Vitamin C with Naproxen rescue
900 mg vitamin C taken orally twice a day (one in the morning and one in the evening) for a 7-day period after ED discharge for the treatment arm used in combination with extended-release acetaminophen 650 mg two pills every eight hours regularly. Naproxen 500mg as rescue medication if still in pain 60 minutes after treatment with acetaminophen.

Other:
• Acetaminophen and Placebo with Naproxen rescue
Placebo taken orally twice a day (one in the morning and one in the evening) for a 7-day period after ED discharge for the treatment arm used in combination with extended-release acetaminophen 650 mg two pills every eight hours regularly. Naproxen 500mg as rescue medication if still in pain 60 minutes after treatment with acetaminophen.

Locations

Country	Name	City	State
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
Hopital du Sacre-Coeur de Montreal	Hopital de l'Enfant-Jesus, The Ottawa Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daily pain intensity	The daily pain intensity will be measured with validated a 0-100 plasticized visual analog scale (VASp) provided to participants during the initial ED visit and documented in the electronic or paper diary.	Seven days
Secondary	NSAIDs consumption	Consumption of NSAIDs rescue medication after seven days. Numbered in seven-day diary and counted at the one-week questionnaire.	Seven days
Secondary	Pain relief	Participants will be asked each day during the seven-day follow-up if their pain has been adequately relieved during the day (yes or no). This will be reported as a percentage.	Seven days
Secondary	New analgesic prescriptions	Numbered and of new pain medication prescription received during follow-up, even opioids.	Seven days
Secondary	Adverse events	We will document during the one-week questionnaire if any of the following adverse events were experienced during the seven-day period: nausea, vomiting, constipation, dizziness, drowsiness, sweating, weakness, or other adverse events.	Seven days
Secondary	Quality of life improvement at seven days	Quality of life will be evaluated during the one-week interview with the validated 12-Item Short Form Survey (SF-12 questionnaire). Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	Seven days
Secondary	Quantity of Healthcare visits	Participants will be asked about the number of all unscheduled or scheduled healthcare visits related to their initial pain condition during the 1-week questionnaire.	Seven days
Secondary	Prevalence of chronic pain	Questionnaire at 90 days. Chronic pain will be defined as pain intensity of = 4 on the NRS (0-10) persistent or that reoccurs on most days after three months.	90 days
Secondary	Prevalence of complex regional pain syndromes for limb fractures	For participants with limb fractures who are still in pain at 90 days, an in-person visit will be scheduled to evaluate the presence of complex regional pain syndrome as defined by the Budapest criteria, which includes a physical examination.; To make the clinical diagnosis, the following criteria must be met: Continuing pain, which is disproportionate to any inciting event.; Must report at least one symptom in all four of the following categories: Sensory Vasomotor Sudomotor/oedema Motor/trophic; Must display at least one sign at time of evaluation in two or more of the following categories: Sensory Vasomotor Sudomotor/oedema Motor/trophic; There is no other diagnosis that better explains the signs and symptoms.	90 days
Secondary	Quality of life improvement at 90 days	Quality of life will be evaluated during the three-month interview with the validated 12-Item Short Form Survey (SF-12 questionnaire). Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	90 days