Ceftriaxone for Lyme Disease

Overseen By Bindu Balani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hackensack Meridian Health

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Cephalosporin allergy, HIV, others

Compensation: Varies

Number of Visits: 9

Duration: 6 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Lyme disease is a public health crisis in the US. It is estimated that over 400,000 cases occur every year with 10-20% of those infected going on to develop Post-Treatment Lyme disease Syndrome (PTLDS). The goal of this study is to investigate if giving Ceftriaxone every 5 days for about 6 weeks kills the organism that produces persistent Lyme infection. Enrolled participants will be randomized 1:1 receiving either pulse-dosed ceftriaxone or placebo \[dextrose (5% in water), (D5W)\], intravenously. Participants will be evaluated at each of the study visits, and then in a follow-up phase out to 12 months. They will be unblinded at 6 months and those randomized to the placebo group will be offered pulse-dosed ceftriaxone on the same schedule as those randomized to the drug group. All patients will be followed up for a total of 12 months post treatment initiation.

Will I have to stop taking my current medications?

You will need to stop taking antibiotics used to treat Lyme disease, like doxycycline or amoxicillin, for at least 6 weeks before joining the study and remain off them during the treatment phase. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

Is ceftriaxone generally safe for treating Lyme disease?

Ceftriaxone is generally well tolerated in treating Lyme disease, with studies showing it does not usually require stopping 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, especially when used without clear evidence of Lyme disease. ^{1 2 3 4 5}

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

Ceftriaxone is unique for Lyme disease treatment because it is administered intravenously (directly into the vein) and is highly effective even in short courses, which can be more convenient and potentially reduce side effects compared to longer treatments. It is particularly effective for late-stage Lyme disease and cases involving the central nervous system. ^{1 2 6 7 8}

Who Is on the Research Team?

Bindu Balani, MD

Principal Investigator

Hackensack Meridian Health

Are You a Good Fit for This Trial?

This trial is for individuals who have been treated for Lyme disease but continue to experience symptoms, suggesting Post-Treatment Lyme Disease Syndrome (PTLDS). Participants must be able to commit to a 6-week treatment plan with follow-ups extending up to 12 months.

Inclusion Criteria

Ability and willingness to sign informed consent

Available for the study period

I experience fatigue that affects my daily activities.

Exclusion Criteria

Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous treatment with a cephalosporin antibiotic, or severe allergic reaction to penicillins (e.g. anaphylaxis or severe rash with Stevens Johnson syndrome or similar)

I am not pregnant or breastfeeding.

I have had a Clostridium difficile infection before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pulse-dosed ceftriaxone or placebo intravenously every 5 days for approximately 6 weeks

6 weeks

9 visits (in-person)

Unblinding

Participants are unblinded at 6 months, and those in the placebo group are offered ceftriaxone

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ceftriaxone

Trial Overview The study is testing the effectiveness of Ceftriaxone, an antibiotic, given every five days over six weeks against a placebo. Patients are randomly assigned in equal numbers and will not know which group they're in until after six months.

How Is the Trial Designed?

Group I: Ceftriaxone 2 GM Experimental Treatment 1 Intervention

Administration of IV ceftriaxone or D5W. Subjects will be infused approximately every 5 days (+/- 1 day) over the course of \~6 weeks. Subjects will receive a total of 9 infusions throughout the treatment phase of the study, with the last infusion tentatively scheduled for Day 41 (+/- 3 days).

Group II: Placebo Placebo Group 1 Intervention

Placebo \[dextrose (5% in water), (D5W)\] IV following the same infusion schedule as the ceftriaxone arm.

Who Is Running the Clinical Trial?

Hackensack Meridian Health

Lead Sponsor

Trials

141

Recruited

42,900+

Columbia Clinical Trials Network for Lyme and Other Tick-Borne Diseases

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

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

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

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

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

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

Ceftriaxone in the treatment of Lyme neuroborreliosis. [2022]

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

Adjuvanted Lyme disease vaccine: a review of its use in the management of Lyme disease. [2018]

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

Use of third-generation cephalosporins. Spirochetes. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Austria pubmed.ncbi.nlm.nih.gov

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