Ceftriaxone for Chronic Lyme Disease

Overseen By Keely Terrillion

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: State University of New York - Upstate Medical University

Must not be taking: Warfarin

Disqualifiers: Pregnancy, Cephalosporin allergy, HIV, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 6 weeks

44 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop taking antibiotics used to treat Lyme disease, such as doxycycline, amoxicillin, cefuroxime, azithromycin, ceftriaxone, or penicillin, for at least 6 weeks before joining and remain off them during the study. If you are taking other medications, the protocol does not specify, so it's best to discuss with the study team.

What data supports the effectiveness of the drug ceftriaxone for chronic Lyme disease?

Research shows that ceftriaxone is effective in treating late-stage Lyme disease, with most patients showing improvement. In studies, patients with Lyme arthritis and neuroborreliosis (a nervous system infection) responded well to ceftriaxone, with many experiencing significant improvement or complete recovery. ^{1 2 3 4 5}

Is ceftriaxone safe for treating Lyme disease?

Ceftriaxone is generally safe for treating Lyme disease, as studies show it is well tolerated with no need to stop treatment due to side effects. However, there are rare cases where serious complications like low white blood cell count, fever, liver issues, and diarrhea have occurred. ^{2 3 6 7 8}

How does the drug Ceftriaxone differ from other treatments for chronic Lyme disease?

Ceftriaxone is unique for chronic Lyme disease because it is an antibiotic given through an IV (intravenous, meaning directly into the vein), which allows it to reach higher concentrations in the body compared to oral antibiotics. This can be particularly useful for treating more severe or persistent cases of Lyme disease. ^{9 10 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to learn if an FDA approved drug, Ceftriaxone, given intermittently, can treat people between 18 and 75 years old with a history of Lyme disease, who are still experiencing persistent or returning symptoms after they have completed treatment. The main questions it aims to answer are: * Will giving Ceftriaxone approximately every 5 days for 6 weeks be safe and well tolerated when compared to a group that receives placebo (a look-alike substance that contains no drug)? * Will giving Ceftriaxone improve symptoms? Participants will be asked to do the following: * Come to the clinic approximately every 5-6 days to receive an IV infusion of either the Ceftriaxone or placebo. * Answer questions about their level of tiredness, body pain, general health and physical ability, sleep, anxiety, depression and any suicidal thoughts. * Give blood so we can make sure your body is handling the drug okay or to help us learn more about how the drug is affecting the persistent Lyme disease symptoms.

Research Team

Kristopher Paolino, MD

Principal Investigator

State University of New York - Upstate Medical University

Eligibility Criteria

This trial is for adults aged 18-75 who have had Lyme disease and are still feeling sick after treatment. They must be able to come to the clinic every 5-6 days for an IV infusion and answer health questions.

Inclusion Criteria

Ability and willingness to sign informed consent

Available for the study period

I experience fatigue that affects my daily activities.

Exclusion Criteria

Patients with a diagnosis of Lyme disease based on only a positive Lyme IgM immunoblot

Planned travel during the study period that would interfere with the ability to complete all study visits (this can be a temporary exclusion with plan to schedule enrollment during a window of time during which they could attend their study visits)

Unable to comply with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV infusion of Ceftriaxone or placebo approximately every 5 days for 6 weeks, totaling 9 treatments

6 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits at 1 month, 3 months, and 6 months from study start

6 months

3 visits (in-person)

Open-label extension

Study unblinded at 6 months; placebo group invited to repeat study with Ceftriaxone, original Ceftriaxone group receives phone follow-up at 1 year

1 year

Treatment Details

Interventions

• Ceftriaxone

Trial Overview The study tests if Ceftriaxone, given every five days over six weeks, is safe and can improve symptoms of persistent Lyme disease compared to a placebo (a substance with no drug).

Participant Groups

Group I: Ceftriaxone Active Control 1 Intervention

Participants will receive IV infusion of 2g Ceftriaxone, approximately every 5 days for 6 weeks for a total of 9 treatments.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive IV infusion of dextrose 5% in water, approximately every 5 days for 6 weeks for a total of 9 treatments

Ceftriaxone is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Rocephin for:

• Sepsis
• Bacterial infections
• Meningitis
• Gonorrhea
• Pelvic inflammatory disease

Approved in United States as Rocephin for:

• Sepsis
• Bacterial infections
• Meningitis
• Gonorrhea
• Pelvic inflammatory disease
• Lower respiratory tract infections
• Skin and skin structure infections
• Urinary tract infections

Approved in Canada as Rocephin for:

• Sepsis
• Bacterial infections
• Meningitis
• Gonorrhea
• Pelvic inflammatory disease
• Lower respiratory tract infections
• Skin and skin structure infections
• Urinary tract infections

Who Is Running the Clinical Trial?

State University of New York - Upstate Medical University

Lead Sponsor

Trials

176

Recruited

27,600+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

10

Recruited

320+

Findings from Research

In a study of 23 patients with late Lyme disease, ceftriaxone was significantly more effective than penicillin, with only 1 out of 13 patients experiencing treatment failure compared to 5 out of 10 with penicillin.

Further treatment with ceftriaxone at doses of 4 g/day or 2 g/day showed similar success rates, suggesting that ceftriaxone is a reliable option for treating late Lyme disease, especially in patients who have not previously received corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of late Lyme borreliosis--randomised comparison of ceftriaxone and penicillin. Dattwyler, RJ., Halperin, JJ., Volkman, DJ., et al.[2019]

In a study of 35 patients with late-stage Lyme borreliosis treated with a 14-day course of ceftriaxone, 73% showed complete response or marked improvement after 36 months, indicating the treatment's efficacy.

Ceftriaxone was well tolerated, with no patients needing to discontinue treatment due to adverse reactions, highlighting its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results in patients with Lyme arthritis following treatment with ceftriaxone. Valesová, H., Mailer, J., Havlík, J., et al.[2019]

In a clinical trial involving 46 patients with neuroborreliosis, a 14-day treatment with 2 g of ceftriaxone once daily resulted in a 30% cure rate at the end of treatment and an 85% cure rate after 9 months for those with early Lyme neuroborreliosis.

The treatment was generally safe, with no patients needing to stop due to adverse reactions, although one patient died from a cardiac infarction unrelated to the antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone in the treatment of Lyme neuroborreliosis. Rohácová, H., Hancil, J., Hulinská, D., et al.[2022]

In a double-blind study of 60 patients with inflammatory arthritis, 19 out of 40 patients treated with ceftriaxone showed improvement, suggesting that some cases of chronic inflammatory arthritis may respond to antibiotic therapy, potentially indicating a bacterial origin.

Despite the initial positive response, 16 of the 27 patients who improved experienced a worsening of their arthritis 6 to 18 months later, highlighting the need for further research into the long-term effects and underlying causes of chronic inflammatory arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone therapy of chronic inflammatory arthritis. A double-blind placebo controlled trial. Caperton, EM., Heim-Duthoy, KL., Matzke, GR., et al.[2022]

Doxycycline is as effective as ceftriaxone for treating chronic Lyme borreliosis with central nervous system symptoms, based on a study of 46 patients over a 12-month follow-up period.

Doxycycline is significantly cheaper than ceftriaxone, although it may cause more gastrointestinal symptoms and photosensitivity reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline versus ceftriaxone for the treatment of patients with chronic Lyme borreliosis. Ogrinc, K., Logar, M., Lotric-Furlan, S., et al.[2018]

A 58-year-old male with Lyme disease initially treated with oral doxycycline showed no improvement, indicating that some patients may not respond to standard treatment.

The patient's symptoms improved significantly after switching to intravenous ceftriaxone, suggesting that alternative treatments may be necessary for refractory cases of Lyme disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Chronic Symptoms of Lyme Disease With Intravenous Ceftriaxone. Naeem, M., Enos, D., Shah, S., et al.[2021]

Ceftriaxone is highly effective against Lyme disease, with a minimum bactericidal concentration (MBC) of 0.050 microg/ml for Borrelia burgdorferi, the bacteria causing the disease.

In a study with C3H mice, a 5-day regimen of ceftriaxone (50 mg/kg/dose) was 100% effective in sterilizing infected tissues, suggesting that shorter antibiotic courses could be effective for treating early uncomplicated Lyme disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of short-course ceftriaxone therapy for Borrelia burgdorferi infection in C3H mice. Pavia, C., Inchiosa, MA., Wormser, GP.[2021]

A case study highlights the risks of empiric antibiotic treatment in patients suspected of having Lyme disease, as a patient treated with intravenous ceftriaxone developed serious complications despite negative tests for the disease.

The complications included granulocytopenia, fever, hepatitis, and Clostridium difficile-associated diarrhea, emphasizing the need for physicians to carefully consider the risks of treating without definitive evidence of Lyme disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening complications of empiric ceftriaxone therapy for 'seronegative Lyme disease'. Nadelman, RB., Arlin, Z., Wormser, GP.[2019]

From 1993 to 2010, the primary medications for managing lupus erythematosus (LE) remained largely unchanged, with prednisone and hydroxychloroquine being the most frequently prescribed treatments by various specialists.

The study revealed a shift in prescribing patterns, where hydroxychloroquine became the leading medication from 2005 to 2010, while prednisone dropped to the second position, indicating a potential change in treatment preferences among physicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in the outpatient medication management of lupus erythematosus in the United States. Sugai, DY., Gustafson, CJ., De Luca, JF., et al.[2015]

Effective management of cutaneous lupus erythematosus (CLE) relies heavily on sun protection and the use of antimalarial agents as first-line treatments, particularly for discoid and subacute forms of the disease.

For chronic and refractory cases, systemic immunosuppressive agents and local corticosteroids are crucial, with thalidomide being a valuable option for difficult cases, although it has significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous lupus erythematosus: diagnosis and management. Fabbri, P., Cardinali, C., Giomi, B., et al.[2018]

The case highlights the occurrence of erysipelas as a complication in a patient with chronic discoid lupus erythematosus (CDLE) affecting the face, emphasizing the need for careful monitoring in such patients.

The review discusses the evolving patterns and clinical features of erysipelas, suggesting that healthcare providers should be aware of these changes for better diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erysipelas complicating chronic discoid lupus erythematosus of the face--a case report and review of erysipelas. Keefe, M., Wakeel, RA., Kerr, RE.[2019]

A 61-year-old woman with systemic lupus erythematosus developed facial erysipelas, which was initially misdiagnosed as a lupus flare, highlighting the importance of accurate diagnosis in patients with complex medical histories.

The patient improved significantly with intravenous antibiotics and a rapid tapering of corticosteroids, demonstrating that appropriate treatment is crucial for conditions that may mimic lupus flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A red face in a lupus patient: thinking beyond lupus rash. Stubbe, M., Smith, V., Thevissen, K., et al.[2016]

The patient with subacute cutaneous lupus erythematosus exhibited severe skin symptoms and low complement levels, indicating an autoimmune response, as confirmed by skin biopsy and immunofluorescence studies.

Initial treatments including prednisolone, chloroquine, cyclosporine, and gold were ineffective, but the condition was successfully managed with dapsone and a higher dose of prednisolone, highlighting the importance of treatment adjustments in autoimmune skin diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy. Tsutsui, K., Imai, T., Hatta, N., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment of late Lyme borreliosis--randomised comparison of ceftriaxone and penicillin. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Long-term results in patients with Lyme arthritis following treatment with ceftriaxone. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Ceftriaxone in the treatment of Lyme neuroborreliosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ceftriaxone therapy of chronic inflammatory arthritis. A double-blind placebo controlled trial. [2022]

5. Austria pubmed.ncbi.nlm.nih.gov

Doxycycline versus ceftriaxone for the treatment of patients with chronic Lyme borreliosis. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Management of Chronic Symptoms of Lyme Disease With Intravenous Ceftriaxone. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of short-course ceftriaxone therapy for Borrelia burgdorferi infection in C3H mice. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Life-threatening complications of empiric ceftriaxone therapy for 'seronegative Lyme disease'. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Trends in the outpatient medication management of lupus erythematosus in the United States. [2015]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Cutaneous lupus erythematosus: diagnosis and management. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Erysipelas complicating chronic discoid lupus erythematosus of the face--a case report and review of erysipelas. [2019]

12. England pubmed.ncbi.nlm.nih.gov

A red face in a lupus patient: thinking beyond lupus rash. [2016]

13. United States pubmed.ncbi.nlm.nih.gov

Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy. [2019]