Symptomatic Management of Lyme Arthritis

NCT04038346 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: STUDY20040185
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Lyme arthritis resolves with appropriate antimicrobial treatment in a majority of patients, but 10-20% of patients develop antibiotic-refractory Lyme arthritis with prolonged arthritis symptoms and treatment courses. Excessive up-regulation of the inflammatory process has been shown in patients with antibiotic-refractory Lyme arthritis. The over-expressed pro-inflammatory cell mediators are downstream of NSAID inhibition, which would suggest initial inflammatory inhibition may be beneficial in these patients. While NSAIDs are known to reduce pro-inflammatory cell mediators early in the course of inflammation, research has shown that there are other cytokines that play a role in the healing after inflammation that are also inhibited by NSAIDs, and that NSAID use can delay healing. It is not known if scheduled NSAID therapy will reduce, increase, or have no effect on the occurrence of refractory Lyme arthritis cases. The hypothesis of the study is that prescribing scheduled NSAIDs at the time of diagnosis of Lyme arthritis can prevent the development of the excessive inflammatory phase and decrease the number of patients with antibiotic-refractory Lyme arthritis, or at least decrease the duration of persistent Lyme arthritis symptoms. The pilot study design randomizes patients to scheduled NSAIDs, scheduled acetaminophen, or scheduled NSAIDs x 1 week than acetaminophen. Primary outcomes are duration of arthritis symptoms, number of refractory cases, side effects and compliance.

Conditions

Lyme Arthritis; Lyme Disease; Arthritis

Keywords

Lyme Arthritis; Lyme; Lyme Disease; Arthritis; NSAID

Outcome Measures

Primary Outcomes (5)

• Joint Pain Reported by Serial Visual Analog Scale (VAS) for Pain Via Text Surveys

  0-100 scale (no pain to worst pain - higher score, worse outcome), slide bar in text survey

  days 0(enrollment), 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected

• Joint Redness Reported by Serial Visual Analog Scale for Joint Redness Via Text Surveys

  0-100 scale (no redness to maximal redness- higher score, worse outcome), slide bar in text survey

  days 0 (enrollment), 1, 3, 7, 10, 14, 21, 28, 60 the VAS score for join redness will be collected

• Joint Movement Reported by Serial Visual Analog Scale for Joint Movement Via Text Surveys

  0-100 scale (no joint movement to normal joint movement- higher score, better outcome), slide bar in text survey

  days 0 (enrollment), 1, 3, 7, 10, 14, 21, 28, 60 the VAS score for joint movement will be collected

• Overall Function Reported by Serial Visual Analog Scale for Overall Function Via Text Surveys

  0-100 scale (severely impaired function to normal function- higher score, better outcome), slide bar in text survey

  days 0 (enrollment), 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected

• Time to Complete Symptom Resolution as Collected by a Yes/no Question on the Text Survey

  If patient answers yes to symptoms completely resolved, the time frame from enrollment will be the days to symptom resolution

  Symptom resolution recorded (days 0, 1, 3, 7, 10, 14, 21, 28, 60) once they enter "yes" to symptoms completely resolved

Secondary Outcomes (4)

• Medication Compliance as Determined by Question in Serial Text Survey

  days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)

• The Number of Participants With Reported Medication Side Effects as Determined by Question in Serial Text Survey

  days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)

• The Number of Participants Who Reported Taking Other Medications as Determined by Question in Serial Text Survey

  days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)

• Number of Participants Who Reported Fever as Determined by Question in Serial Text Survey

  days 0 (enrollment), 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)

Other Outcomes (1)

• Need for Further Care as Determined by Medical Record Review as Mean Number of Visits in the System for Lyme Arthritis Symptoms During Each Time Frame

  30 days, 60 days, 120 days, 1 year

Study Arms (4)

NSAID

EXPERIMENTAL

Naproxen at weight based standard dose given bid daily until symptoms resolve

Drug: Naproxen

Acetaminophen

ACTIVE COMPARATOR

Acetaminophen at weight based standard dose given qid until symptoms resolve

Drug: Acetaminophen

NSAID first, then Acetaminophen

EXPERIMENTAL

Naproxen at weight based standard dose given bid for one week, then acetaminophen at weight based standard dose given qid until symptoms resolve

Drug: Naproxen; Drug: Acetaminophen

Standard Care

NO INTERVENTION

Symptom observation only

Interventions

Naproxen DRUG

Patients will be randomized to an NSAID (naproxen)

Also known as: naprosyn, aleve, anaprox

NSAID; NSAID first, then Acetaminophen

Acetaminophen DRUG

Patients will be randomized to acetaminophen

Also known as: tylenol

Acetaminophen; NSAID first, then Acetaminophen

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Arthritis
• Undergoing Lyme disease testing (Lyme test positive)

You may not qualify if:

• Patients will be secondarily withdrawn from analysis and instructed to stop study medication if their Lyme test is negative.
• Underlying diagnosis of rheumatoid or recurrent arthritis Already on scheduled NSAIDs
• Anything that restricts the prescription of naproxen or acetaminophen:
• Hypersensitivity to naproxen (for example: anaphylactic reactions, serious skin reactions) or any component of the formulation; history of aspirin induced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs, underlying kidney or liver impairment
• Already taking daily NSAIDs (naproxen or ibuprofen) or daily acetaminophen
• Hypersensitivity to acetaminophen or any component of the formulation; severe liver impairment or severe active liver disease

Sponsors & Collaborators

• Desiree Neville, MD: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Lyme Disease; Arthritis

Interventions

Naproxen; Acetaminophen

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases; Joint Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Limitations and Caveats

The study was stopped prematurely due to Covid research pause and then overlapping study populations.

Results Point of Contact

• Title: Desiree Neville
• Organization: University of Pittsburgh Children's Hospital of Pittsburgh

desiree.neville@chp.edu

412-692-7692

Study Officials

• Desiree NW Neville, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatric Emergency Medicine

Model Details: Prospective, randomized, controlled, non blinded

Study Record Dates

• First Submitted: July 15, 2019
• First Posted: July 30, 2019
• Study Start: October 1, 2019
• Primary Completion: May 12, 2025
• Study Completion: May 12, 2025
• Last Updated: November 17, 2025
• Results First Posted: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)