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?

This trial tests whether Ceftriaxone, administered every five days for about six weeks, can effectively treat persistent Lyme disease. Lyme disease poses a serious health issue, and some individuals continue to experience symptoms even after standard treatments. Participants will receive either Ceftriaxone or a placebo (a harmless substance like sugar water) to determine if the drug offers more benefits than no treatment. Individuals who have had Lyme disease and continue to experience fatigue affecting their daily life might be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that patients usually tolerate ceftriaxone well. In one study, 90% of patients with Lyme-related nerve problems responded well to ceftriaxone treatment. Another study found that ceftriaxone was more effective than a placebo and another antibiotic, doxycycline, for treating Lyme disease.

However, antibiotics like ceftriaxone can sometimes cause more side effects than a placebo. While ceftriaxone is generally safe, some people might experience mild to moderate side effects. Prospective trial participants should consider these potential risks and benefits. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Lyme disease?

Researchers are excited about ceftriaxone for Lyme disease because it has a unique delivery method compared to the standard oral antibiotics like doxycycline and amoxicillin. Ceftriaxone is administered intravenously, which could potentially deliver the medication more directly and effectively to the site of infection. This method might improve outcomes, especially in cases where the bacteria are particularly persistent or when neurological symptoms are present. Furthermore, the infusion schedule is designed to maintain consistent therapeutic levels, possibly enhancing efficacy and patient recovery.

What evidence suggests that ceftriaxone might be an effective treatment for Lyme disease?

Research has shown that ceftriaxone effectively treats Lyme disease. One study found that ceftriaxone worked well for early cases, even when the disease affected the brain or heart. In this trial, participants will receive either ceftriaxone or a placebo. Another study showed that ceftriaxone had better results than a placebo, a fake treatment used for comparison. However, some research indicated that in certain cases, the bacteria causing Lyme disease can survive despite ceftriaxone treatment. Overall, ceftriaxone has helped many people with Lyme disease, but it may not work in every situation. ^{1 4 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

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 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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC126994/

Efficacy of Short-Course Ceftriaxone Therapy for Borrelia ... This study has demonstrated that five doses of ceftriaxone given over either 24 h or 5 days cures B. burgdorferi infection in C3H mice.

2. nejm.org nejm.org/doi/full/10.1056/NEJM199707313370501

Ceftriaxone Compared with Doxycycline for the Treatment ... Treatment with ceftriaxone is effective in acute disseminated Lyme disease, including that manifested by neuroborreliosis, carditis, and meningitis.

3. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-07989-4

Efficacy and safety of antibiotic therapy for post-Lyme disease ... The network meta-analysis showed that ceftriaxone had better results than placebo [Mean = 0.87, 95% CI (0.02, 1.71)] and doxycycline [Mean = ...

4. hopkinslyme.org hopkinslyme.org/lyme-disease/treatment-and-prognosis-of-lyme-disease/

Lyme Disease Treatment and Prognosis The results confirm that a Lyme disease infection can trigger PTLD despite early treatment with 21 days of the antibiotic doxycycline. This rigorously designed ...

5. academic.oup.com academic.oup.com/jid/article/195/10/1489/2191936

Anti—Tumor Necrosis Factor—α Treatment Activates Borrelia ... In summary, our results show that B. burgdorferi is able to evade the killing effect of ceftriaxone in this mouse model of Lyme borreliosis.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8852482/

Long-term Results in Patients With Lyme Arthritis Following ... The treatment results in this group of 35 patients with Lyme arthritis are considered successful. The data obtained are consistent with expectations based on ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06611111

Ceftriaxone Pulse Dose for Post-Treatment Lyme Disease 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 ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/ene.16293

Treatment of post‐treatment Lyme disease symptoms—a ... Meta-analysis of safety outcomes showed statistically significantly more adverse events for antibiotics compared to placebo. ... data on efficacy ...