Immunogenicity and safety of the 20-Valent pneumococcal conjugate vaccine (PCV-20) administered during an acute febrile illness in adults: a multicentre randomized non-inferiority trial: PREV-HOSPIT
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 1,160
- 试验地点
- 21
- 主要终点
- Proportion of immune “good responders” to PCV-20 at 1 month after vaccination in both arms. Immune“Good responders” are defined by both of the following criteria : a seroconversion (a 2-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA,AND an immune protective response defined as ELISA IgG > 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.
研究概览
简要总结
To demonstrate that the immune response at one month after 20-valent pneumococcal conjugate vaccine (PCV-20) administered during an acute febrile illness is non-inferior to the immune response obtained at one month after PCV-20 administered 15-58 days after resolution of the acute febrile illness in unvaccinated patients at high and medium risk for pneumococcal infections.
研究设计
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None (Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and <85 years-old
- •History of body temperature ≥ 38°C measured at least twice prior to randomization (Randomization must be performed as soon as possible on a febrile patient or 72 hours after apyrexia at the latest)
- •Having at least one comorbidity that defines patients as medium or high risk for pneumococcal invasive infection: · Medium risk: Cyanogenic congenital heart disease; chronic heart failure; chronic cardiopathy; chronic respiratory failure; chronic obstructive pulmonary disease; emphysema; severe asthma under chronic treatment; chronic renal failure; chronic liver disease; diabetes mellitus treated; Osteo-meningeal leak or cochlear implant · High risk : Hypo or asplenic people; hereditary immunodeficiency syndromes; people living with HIV; solid organ transplanted; People under immunosuppressors (corticosteroids, biotherapy) for an auto-immune or an inflammatory chronic disease; patients with nephrotic syndrome
- •Hospitalization for > 24 hours long
- •Social security affiliation
- •Signed informed consent
排除标准
- •Patient unable to give informed consent
- •S. pneumoniae infection with laboratory confirmation (blood culture, culture from a sterile site, urinary or Cerebrospinal fluid antigens, sputum culture with > 10^7 CFU/mL), if available and if the result is known before randomization.
- •Curatorship, wardship
- •History of previous vaccination with PCV-7 or PCV-13 or PCV-20
- •History of PPV-23 in the previous year
- •Patient having received another vaccination within one month prior to inclusion or planning another vaccination in the month after inclusion except for Influenza vaccine.
- •Patient with history of bone marrow transplantation
- •Patient with haemotological malignancies
- •Patient under chemotherapy for solid tumor or with a history of chemotherapy in the past three months
- •Patient treated with Rituximab currently or in the past 6 months
- •People with no command of the French language
- •Patient with qSOFA score ≥ 2 at randomization (acute severe febrile illness)
- •Patient hospitalized in an Intensive Care Unit
- •Breastfeeding woman
- •Recipients of polyclonal gammaglobulins in the past three months
- •Inability to follow the protocol
- •Bleeding disorder contra-indicating intramuscular injection according to the investigator
- •History of allergy to PCV-20 or vaccine-related components.
结局指标
主要结局
Proportion of immune “good responders” to PCV-20 at 1 month after vaccination in both arms. Immune“Good responders” are defined by both of the following criteria : a seroconversion (a 2-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA,AND an immune protective response defined as ELISA IgG > 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.
Proportion of immune “good responders” to PCV-20 at 1 month after vaccination in both arms. Immune“Good responders” are defined by both of the following criteria : a seroconversion (a 2-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA,AND an immune protective response defined as ELISA IgG > 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.
OR a seroconversion (a 4-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG < 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.
OR a seroconversion (a 4-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG < 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.
次要结局
- Safety endpoints in both arms in the month following vaccination: Number, type and severity of adverse events Frequency of local reactions Frequency of systemic events related to the vaccination
- Proportion of immune good responders serotype by serotype at one month post vaccination (ELISA 2-fold increase and ELISA IgG > 1,3μg/mL).
- OPA IgG titers for serotype by serotype at one month post vaccination in both groups measured a posteriori among immune good responders
- Proportion of the participants immune “good responders” to PCV-20 in both arms, at 1 year after vaccination. “Good responders” being defined above (primary end-point)
- Number of low respiratory tract infections events in both arms until one year after inclusion.
- Number of confirmed S.pneumoniae infections in both arms until one year after inclusion
- Description of richness and diversity of gut microbioma before vaccination associated with people qualified as immune good responders in both arms
- Fold change kinetics (transcriptomics) (before and at 24 hours after vaccination) of vaccine-induced gene signatures in peripheral blood mononuclear cells and serum cytokine levels at baseline and 24 hours after vaccination in both arms.
- Frequency of specific PCV-20 IFNg secreting CD4 or CD8 T cells in both arms at one month post vaccination
- Frequency of specific PCV-20 IFNg secreting CD4 or CD8 T cells in both arms at one year post vaccination
- Proportion of volunteers with circulatory IgA (specific of pneumococcus) in both arms at one month post vaccination
研究者
Pr. Elisabeth BOTELHO-NEVERS
Scientific
Centre Hospitalier Universitaire De Saint Etienne