Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Desiree Neville, MD
Must not be taking: Daily NSAIDs, Daily acetaminophen
Disqualifiers: Rheumatoid arthritis, Kidney impairment, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing if taking anti-inflammatory drugs regularly can help prevent long-term joint problems in people with Lyme disease. It focuses on patients who don't get better with antibiotics. The drugs work by reducing inflammation, which might stop the prolonged symptoms.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but if you are already taking daily NSAIDs or acetaminophen, you cannot participate. If you have any hypersensitivity to naproxen or acetaminophen, you should not take the study medications.
What evidence supports the effectiveness of the drug naproxen for treating Lyme arthritis?
Research shows that naproxen, a type of anti-inflammatory drug, is effective in relieving pain for conditions like rheumatoid arthritis, which is similar to Lyme arthritis. It was found to provide significant pain relief and was preferred by patients in studies comparing it to other pain relievers.
12345Is naproxen sodium safe for general use?
Naproxen sodium is generally safe for over-the-counter use, with most people experiencing no adverse effects. Common side effects include headache, nausea, and drowsiness, but these occur at similar rates to a placebo. However, it can cause stomach issues, allergic reactions, and liver problems, and should be avoided by people with heart failure or high blood pressure.
678910How does the drug Acetaminophen and Naproxen differ from other treatments for Lyme Arthritis?
Acetaminophen and Naproxen are used for their pain-relieving and anti-inflammatory effects, with Naproxen being a nonsteroidal anti-inflammatory drug (NSAID) that reduces inflammation and pain, while Acetaminophen primarily relieves pain and reduces fever. This combination may offer a balanced approach to managing symptoms of Lyme Arthritis, especially for patients who cannot tolerate other anti-inflammatory drugs like aspirin.
311121314Eligibility Criteria
This trial is for individuals with Lyme arthritis who are testing positive for Lyme disease. It's not suitable for those with rheumatoid or recurrent arthritis, on daily NSAIDs or acetaminophen, have severe liver issues, a history of allergic reactions to NSAIDs, or underlying kidney or liver impairment.Inclusion Criteria
Undergoing Lyme disease testing (Lyme test positive)
I have arthritis.
Exclusion Criteria
Patients will be secondarily withdrawn from analysis and instructed to stop study medication if their Lyme test is negative
I am allergic to naproxen, aspirin, or have had bad reactions to NSAIDs.
I am allergic to acetaminophen or have severe liver problems.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants are randomized to receive scheduled NSAIDs, acetaminophen, or NSAIDs followed by acetaminophen to manage Lyme arthritis symptoms
8 weeks
Regular text surveys on days 1, 3, 7, 10, 14, 21, 28, 60
Follow-up
Participants are monitored for safety and effectiveness after treatment, including symptom resolution and side effects
4 weeks
Follow-up visits as needed based on symptom resolution
Long-term Follow-up
Participants' need for further care and medication compliance are assessed over an extended period
1 year
Participant Groups
The study tests if scheduled use of the anti-inflammatory drug Naproxen, pain reliever Acetaminophen, or a combination can prevent prolonged symptoms in Lyme arthritis. Patients will be randomly assigned to one of these treatments and monitored for symptom duration and treatment side effects.
4Treatment groups
Experimental Treatment
Active Control
Group I: NSAID first, then AcetaminophenExperimental Treatment2 Interventions
Naproxen at weight based standard dose given bid for one week, then acetaminophen at weight based standard dose given qid until symptoms resolve
Group II: NSAIDExperimental Treatment1 Intervention
Naproxen at weight based standard dose given bid daily until symptoms resolve
Group III: Standard CareActive Control1 Intervention
Symptom observation only
Group IV: AcetaminophenActive Control1 Intervention
Acetaminophen at weight based standard dose given qid until symptoms resolve
Acetaminophen is already approved in United States, European Union, Canada, Australia for the following indications:
🇺🇸 Approved in United States as Tylenol for:
- Pain relief
- Fever reduction
🇪🇺 Approved in European Union as Paracetamol for:
- Pain relief
- Fever reduction
🇨🇦 Approved in Canada as Tylenol for:
- Pain relief
- Fever reduction
🇦🇺 Approved in Australia as Panadol for:
- Pain relief
- Fever reduction
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's Hospital of Pittsburgh of UPMCPittsburgh, PA
Who Is Running the Clinical Trial?
Desiree Neville, MDLead Sponsor
References
European experience with flurbiprofen. A new analgesic/anti-inflammatory agent. [2022]Numerous European clinical trials begun more than 12 years ago have clearly demonstrated flurbiprofen's safety and efficacy as an analgesic, anti-inflammatory, and antipyretic agent. In preclinical studies, flurbiprofen was at least as potent as indomethacin, and approximately 200 times more potent than aspirin. For patients with rheumatoid arthritis, a review of several trials found flurbiprofen often superior to aspirin and naproxen, and equivalent to indomethacin and ibuprofen in efficacy. Acetaminophen appeared no more effective than placebo for patients with rheumatoid arthritis. For patients with ankylosing spondylitis, flurbiprofen was also shown to be equivalent or superior to indomethacin and phenylbutazone. For patients with osteoarthritis of the peripheral joints, spine, hip, and knee, flurbiprofen was again found equal to ibuprofen, diclofenac, indomethacin, and naproxen. Side effects with flurbiprofen were few and predominantly related to the gastrointestinal tract.
A comparative trial of benoxaprofen and naproxen. [2019]A double-blind within-patient trial in rheumatoid arthritis comparing the new anti-inflammatory drug benoxaprofen with naproxen is reported. Patients received naproxen 250 mg b.d. for two weeks and benoxaprofen 200 mg b.d. for three weeks. Both drugs demonstrated efficacy. There was no statistically significant difference between them, except for grip strength which favoured naproxen. Side-effects were mild, infrequent and similar for both drugs. Evidence is presented which confirms the long duration of action of benoxaprofen, a fact which may be of clinical significance.
Drug therapy reviews: antirheumatic agents. [2013]The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment.
Comparison of the analgesic effect of ten nonsteroidal anti-inflammatory drugs. [2019]The analgesic effect of 10 anti-inflammatory drugs was compared using a single-blind method in 90 patients with rheumatoid arthritis. Each patient received two different drugs, for three days each and each drug was evaluated in 18 patients. After the trial, the patients considered which of the drugs they preferred. The greatest relief from pain was achieved by diclofenac, indomethacin, naproxen and tolfenamic acid, each of these being preferred by the majority of patients and being significantly (p less than 0.01) better than the least effective drugs ketoprofen and proquazone. Acetylsalicylic acid, azapropazone, carprofen and ibuprofen were considered intermediate in efficacy.
Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review. [2018]To systematically review the literature on the efficacy and safety of paracetamol (acetaminophen) in the management of pain in inflammatory arthritis.
Safety profile of over-the-counter naproxen sodium. [2019]The safety of naproxen sodium for over-the-counter use was evaluated based on 48 randomized, double-blind, placebo-controlled clinical trials that evaluated naproxen/naproxen sodium (NAP) for indications appropriate to, and under, conditions common to, nonprescription analgesics. Of the 48 studies, 27 were single-dose studies and 21 were multiple-dose studies of 1 to 10 days' duration; 19 studies included ibuprofen and 9 included acetaminophen. A total of 4138 patients received naproxen or naproxen sodium (3589 patients received naproxen 187.5 to 400 mg and 549 received naproxen sodium 220 to 440 mg), 2423 received placebo, 1574 received ibuprofen (200 or 400 mg), and 671 received acetaminophen (500 to 1000 mg). Adverse-event rates were examined in three sets of comparisons: NAP versus placebo (48 studies); NAP versus ibuprofen and placebo (19 studies); and NAP versus acetaminophen and placebo (9 studies). Across all 48 studies, 83% of both the NAP- and placebo-treated patients reported no adverse events. The incidence rates were similar between NAP and placebo, with headache (4.8% NAP, 6.4% placebo), nausea (3.4% NAP, 3.1% placebo), and somnolence (2.7% NAP, 1.9% placebo) the most commonly reported events. Rates of adverse events with NAP, ibuprofen, and acetaminophen were similar.
Naproxen sodium. [2019]Naproxen sodium possesses analgesic, antipyretic, and anti-inflammatory effects. Adverse effects of naproxen sodium include gastrointestinal effects, precipitation of allergic symptoms, and potential for hepatotoxicity. Naproxen sodium is contraindicated in patients with known sensitivity and those with heart failure, hypertension, or other conditions associated with fluid retention. Nonprescription products of naproxen sodium, ibuprofen, ketoprofen, acetaminophen, and salicylates are all similarly effective in treating mild aches and pains and reducing fever.
Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the treatment of acute migraine. [2013]To evaluate the long-term safety and tolerability of sumatriptan-naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose.
Naproxen: pharmacology and dental therapeutics. [2022]Naproxen and naproxen sodium are very commonly used and effective non-steroidal anti-inflammatory analgesics. In this paper, they are described and compared, and their pharmacokinetics and indications are discussed. Adverse reactions to these drugs and the mechanism of action of these effects on the gastrointestinal tract, central nervous system, kidneys, liver, and blood are described. A discussion of the effects of the drugs on the elderly and during pregnancy and lactation is included. Also, the allergenicity, miscellaneous rare complications and acute toxicity of the naproxen anion are described, followed by a description of the more common drug interactions. The results of several recent studies that may call into question the current recommendations on using these pharmaceuticals are cited. Until this controversy can be resolved, the practitioner should rely on the principle of "first do no harm" in choosing a course of drug treatment.
Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. [2023]Following the paucity of safety reports in the use of Artemisinin-Based Combination Therapies (ACTs) plus paracetamol, the study assessed safety potential of artemether-lumefantrine (ALP), artesunate-amodiaquine (AAP), artesunate-mefloquine (AMP), artesunate-sulphadoxine-pyrimethamine (ASPP) and dihydroartemisinin-piperaquine (DHPP) combination with paracetamol in malaria patients.
A comparative study of Butacote and Naprosyn in ankylosing spondylitis. [2019]A double-blind, cross-over comparison of Naprosyn (naproxen) 750 mg daily and Butacote (enteric-coated phenylbutazone) 300 mg daily was carried out in a multi-centre trial. Twenty-five patients, mostly male and under 40 years of age, were entered. After a 2-week period in which any existing anti-inflammatory drugs were tailed off, patients were entered into the trial and treated for 1 month with each drug. Patients were assessed at 4-weekly intervals. Both drugs significantly reduced morning stiffness. Morning pain and discomfort and wall-tragus distance were also significantly reduced by both drugs during the trial. Results of the Schober test showed improvement during both treatment periods. There were no overall statistically significant differences between the effects of the 2 drugs on objective parameters. However, overall subjective assessment of symptoms showed a greater improvement on Butacote. Treatment preferences by physician and subjective assessment by the patient both favoured Butacote but the difference between the 2 drugs was not statistically significant. Side effects were mostly of a minor nature. One patient had to discontinue the trial, due to indigestion while taking Butacote.
Dipyrone elicits substantial inhibition of peripheral cyclooxygenases in humans: new insights into the pharmacology of an old analgesic. [2015]Dipyrone (INN, metamizol) is a common analgesic used worldwide. Its widespread prescription or over-the-counter use in many countries (e.g., Brazil, Israel, Mexico, Russia, Spain) requires insight into its mode of action. This study therefore addressed the impact of its metabolites 4-methyl-amino-antipyrine (MAA) and 4-amino-antipyrine (AA) on peripheral cyclooxygenases (COX). Pharmacokinetics of metabolites and ex vivo COX inhibition were assessed in five volunteers receiving dipyrone at single oral doses of 500 or 1000 mg. Coagulation-induced thromboxane B2 formation and lipopolysaccharide-induced prostaglandin E2 synthesis were measured in vitro and ex vivo in human whole blood as indices of COX-1 and COX-2 activity. In vitro, metabolites elicited no substantial COX-1/COX-2 selectivity with MAA (IC50=2.55 micromol/L for COX-1; IC50=4.65 micromol/L for COX-2), being approximately 8.2- or 9-fold more potent than AA. After administration of dipyrone, MAA plasma concentrations remained above the IC50 values for each isoform for at least 8 h (500 mg) and 12 h (1000 mg) postdose. COX inhibition correlated with MAA plasma levels (ex vivo IC50 values of 1.03 micromol/L [COX-1] and 0.87 micromol/L [COX-2]). By contrast, plasma peak concentrations of AA after the 1000 mg dose were 2.8- and 6.5-fold below its IC50 values for COX-1 and COX-2, respectively. Maximal inhibitions of COX-1 and COX-2 were 94% and 87% (500 mg), 97% and 94% (1000 mg). Taken together, dipyrone elicits a substantial and virtually equipotent inhibition of COX isoforms via MAA. Given the profound COX-2 suppression by dipyrone, which was considerably above COX-2 inhibition by single analgesic doses of celecoxib and rofecoxib, a significant portion of its analgesic action may be ascribed to peripheral mechanisms. In view of the observed COX-1 suppression, physicochemical factors (lack of acidity) rather than differential COX-1 inhibition may be responsible for dipyrone's favorable gastrointestinal tolerability compared with acidic COX inhibitors.
Different mechanisms underlie the analgesic actions of paracetamol and dipyrone in a rat model of inflammatory pain. [2018]The analgesics, paracetamol and dipyrone are weak inhibitors of the cyclooxygenase isoforms 1 or 2 (COX-1, COX-2) but more potent on COX-3. Both are also weak anti-inflammatory agents, relative to their analgesic and antipyretic activities. In a model of inflammatory pain mediated by prostaglandins, both compounds were analgesic. We have analysed this shared effect further in order to elucidate the underlying mechanisms.
The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: a critical review. [2018]The aim of this review was to assess the value of NSAIDs and paracetamol in patients with cancer pain to update a previous review performed ten years ago on this topic. The approach was analytic and based on clinical considerations, rather than on raw evidence, which often does not provide useful information in clinical practice. Both published reports from an extensive search of electronic data bases were collected from January 2001 to December 2011. A free-text search method was used including the following words and their combination: "Anti-inflammatory drugs OR paracetamol OR acetaminophen" AND/OR "cancer pain". Any randomized-controlled trial was considered. Thirteen reports fulfitted inclusion criteria in this systematic review. Randomized trials have been performed by using different modalities of intervention. Single drugs added on opioid therapy or during opioid substitution with opioids as rescue drugs through a patient controlled analgesia, were compared with placebo or between them. Five studies regarded paracetamol. Other four studies assessed the efficacy dipyrone, ketorolac, dexketoprofen, and subcutaneous ketoprofen in cancer pain management, mainly on top of an opioid regimen. The role of paracetamol and NSAIDs in the management of cancer pain still remains controversial. The papers published in this last decade were unable to answer the main questions. There is no proof that they should be used to start the treatment and how long they should be administered when opioid treatment is added on top. While paracetamol seems to be devoid of any benefit, particularly if given at usual clinical doses which should be less than 4 g/day, ketorolac seems to provide an additive analgesic effect even in patients receiving different doses of opioids. The main indication from the analysis of these data is that NSAIDs could be given in patients receiving opioids, evaluating their benefit and weight on opioid therapy in individual patients who have a favorable response to justify a prolonged use.