Efficacy of Temocillin Compared to Standard of Care in the Treatment of Neisseria Gonorrhoeae Infections : A Multicenter Randomized Controlled Non-Inferiority Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 360
- 试验地点
- 1
研究概览
简要总结
Neisseria gonorrhoeae (Ng) infections are common and increasing in incidence. Treatment with a third generation cephalosporin, i.e ceftriaxone 1g, single dose, intramuscular (IM), is recommended as a first line treatment. Ceftriaxone is a broad-spectrum antibiotic with high impact on the intestinal microbiota associated with the acquisition of multidrug-resistant bacteria, particularly extended spectrum beta lactamase producing Enterobacteracerales (ESBL-E). Among populations at high risk for sexually transmitted infections (STI), the colonization rate of ESBL-E is particularly high, up to 30%, implying (i) a risk of transmission within the community and (ii) a risk of infections caused by multidrug-resistant organisms, which are difficult to treat. Temocillin, a narrow-spectrum antibiotic is known for its low ecological impact, appears to be a highly promising option. Ng strains currently circulating in France appear to be sensitive to it. Thus, temocillin could be as effective as ceftriaxone to treat Ng infections while avoiding the deleterious impact of broad-spectrum β-lactams on the acquisition of multidrug-resistant bacteria by patients
详细描述
Sexually transmitted infections (STIs) are a major global public health issue. Ng infections are highly prevalent, with 100,000 cases reported in Europe in 2023, over 50% in men who have sex with men (MSM). Globally, WHO (World Health Organization) estimated 82.4 million new cases in 2020 among individuals aged 15-49, with incidence rates of 19 per 1000 women and 23 per 1000 men.
In France, Ng infections have been rising since the 2000s, particularly in MSM, with positivity rates 5-6 times higher than in heterosexual men and 7 times higher than in heterosexual women. Infections are mostly asymptomatic (~95%), though urethritis, cervicitis, proctitis, arthritis, and disseminated infections can occur.
Ng rapidly develops antimicrobial resistance due to genetic plasticity. Multidrug-resistant strains have emerged globally, but in France nearly all strains remain ceftriaxone-sensitive, with only 0.2% resistant in 2022. Standard treatment is ceftriaxone 1 g IM, a critical antibiotic impacting microbiota, and the only effective current option. Vaccine development is ongoing: the Bexsero vaccine showed 22% efficacy in reducing infections, and Phase 1/2 trials of Ng-specific vaccines are underway. Vaccine hesitancy and heterogeneous coverage, even in high-risk populations such as HIV (Human Immunodeficiency Virus) positive MSM, may limit rapid impact.
Alternative therapies include antibiotic combinations and new agents such as zoliflodacin, though pharyngeal efficacy is lower and broad-spectrum use is limited due to resistance concerns. Repositioning antibiotics has been explored: gentamicin shows low microbiota impact but lower pharyngeal efficacy; fosfomycin is ineffective for Ng; carbapenems (ertapenem) are effective but reserved for multidrug-resistant cases; temocillin, a narrow-spectrum β-lactam, preserves microbiota and colonization resistance and may improve pharyngeal clearance when given IV (Intravenous) or IM. Patient-centered outcomes, including perceived care quality, speed, and pain, will be assessed using short satisfaction questionnaires.
The main objective of this study is to demonstrate the non-inferiority of 2g IV or IM temocillin treatment compared to the reference treatment with 1g IM ceftriaxone (Standard of Care (SOC)) for Neisseria gonorrhoeae infections at day 21 (negative PCR (Polymerase Chain Reaction) in urine/vagina, throat and/or anus).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Positive PCR for Ng (urine/vagina and/or throat and/or anus)
- •Asymptomatic Neisseria gonorrhoeae infection
- •Patient who has understood the entirety of the study and accepts its constraints
- •Women of child-bearing potential (i.e. fertile, following menarche and until becoming post-menopaused unless permanently sterile) who are sexually active have to apply a effective method of birth control*, throughout the study period and for 90 days following the last dose of study treatment.
- •Signature of the consent form for participation in the trial.
- •Affiliation with a Social Security scheme or State Medical Aid (AME) (waiver to exempt the necessity for patients to be affiliated with a such scheme)
- •French, English or Spanish speaker
排除标准
- •1 - Known allergy to penicillin, temocillin, ceftriaxone or other beta-lactam antibiotics (grade 3 or 4) 2-Known complete heart block 3- Known hypersensitivity to lidocaine or other amide-type anaesthetics 4- Clinical suspicion of hypovolemia 5 - Concomitant antibiotic treatment to be started or in progress for another bacterial infection except for doxycycline as post exposure prophylaxis 6 - BMI (Body Mass Index)> 35 kg/m2 7 - Another ongoing antibiotic therapy < 1 month except for doxycycline as post exposure prophylaxis) 8 - Complicated upper genital infection 9 - Pregnant or breastfeeding woman (urinary βHCG (Beta Human Chorionic Gonadotropin) at baseline for patients with childbearing potential*) 10 - Known renal or hepatic dysfunction 11 - Patient on curative anticoagulation or known haemostasis disorder (contraindication for the IM route) 12- Prior participation in this study 13 - Patient under legal guardianship 14 - Participation in another randomized trial or trial concerning a medicinal product or clinical investigation protocol concerning a medical device (<3 months) 15- patients deprived of liberty by judicial or administrative decision 16- Patients who are the investigator or any other member of the study team, or close relatives of the investigator or persons involved in the study (e.g., assistant physicians, pharmacists, nurses…)*A woman is considered of childbearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
研究组 & 干预措施
A single 1 g dose of IM ceftriaxone
Patients will receive a single 1 g dose of IM ceftriaxone (SOC) after reconstitution with 3.5 mL of lidocaine at 10 mg/mL to prevent pain at the injection site
干预措施: Blood samples: 1 EDTA (Ethylenediaminetetraacetic acid) (7 ml) and 1dry tube (7 ml) (Other)
A single 1 g dose of IM ceftriaxone
Patients will receive a single 1 g dose of IM ceftriaxone (SOC) after reconstitution with 3.5 mL of lidocaine at 10 mg/mL to prevent pain at the injection site
干预措施: Rectal swab for ESBL-E and microbiota (Eswab) (Other)
A single 1 g dose of IM ceftriaxone
Patients will receive a single 1 g dose of IM ceftriaxone (SOC) after reconstitution with 3.5 mL of lidocaine at 10 mg/mL to prevent pain at the injection site
干预措施: Ceftriaxone 1 g intramuscular single dose with lidocaine (3,5ml) (Drug)
A single 1 g dose of IM ceftriaxone
Patients will receive a single 1 g dose of IM ceftriaxone (SOC) after reconstitution with 3.5 mL of lidocaine at 10 mg/mL to prevent pain at the injection site
干预措施: Rectal, throat, urine/vagina swab (Cobas/Panther and eswab) (Other)
A single 2 g dose of IM temocillin
Patients will receive a single 2 g dose of IM temocillin after reconstitution with 3 m L of lidocaine at 10 mg/mL to prevent pain at the injection site.
干预措施: Rectal, throat, urine/vagina swab (Cobas/Panther and eswab) (Other)
A single 2 g dose of IM temocillin
Patients will receive a single 2 g dose of IM temocillin after reconstitution with 3 m L of lidocaine at 10 mg/mL to prevent pain at the injection site.
干预措施: Blood samples: 1 EDTA (Ethylenediaminetetraacetic acid) (7 ml) and 1dry tube (7 ml) (Other)
A single 2 g dose of IM temocillin
Patients will receive a single 2 g dose of IM temocillin after reconstitution with 3 m L of lidocaine at 10 mg/mL to prevent pain at the injection site.
干预措施: Rectal swab for ESBL-E and microbiota (Eswab) (Other)
A single 2 g dose of IM temocillin
Patients will receive a single 2 g dose of IM temocillin after reconstitution with 3 m L of lidocaine at 10 mg/mL to prevent pain at the injection site.
干预措施: Temocillin (NEGABAN®) 2 g intramuscular single dose with lidocaine (3ml) (Drug)
A single 2 g dose of IV temocillin.
Patients will receive a single 2 g dose of IV temocillin diluted in 20 mL of water for injection.
干预措施: Temocillin (NEGABAN®) 2 g intravenous with lidocaine (3ml) (Drug)
A single 2 g dose of IV temocillin.
Patients will receive a single 2 g dose of IV temocillin diluted in 20 mL of water for injection.
干预措施: Rectal swab for ESBL-E and microbiota (Eswab) (Other)
A single 2 g dose of IV temocillin.
Patients will receive a single 2 g dose of IV temocillin diluted in 20 mL of water for injection.
干预措施: Rectal, throat, urine/vagina swab (Cobas/Panther and eswab) (Other)
A single 2 g dose of IV temocillin.
Patients will receive a single 2 g dose of IV temocillin diluted in 20 mL of water for injection.
干预措施: Blood samples: 1 EDTA (Ethylenediaminetetraacetic acid) (7 ml) and 1dry tube (7 ml) (Other)