Acute Febrile IllnessPhase 4PREV-HOSPITNCT06822907
Immunogenicity and Safety PCV-20 of the Vaccine Administered During an Acute Febrile Illness in Adults
A Phase 4 study testing Early intervention and Delayed intervention in people with Acute Febrile Illness and Pneumococcal Infections, run by Centre Hospitalier Universitaire de Saint Etienne at 24 sites in France.
Trial summary
Streptococcus pneumoniae is responsible for serious infections associated to numerous hospitalizations and high rate of mortality. The incidence and therefore the burden of pneumococcal infections have been significantly reduced thanks to the use of pneumococcal conjugate vaccines (PCVs). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Febrile Illness, Pneumococcal Infections
- What is being tested?
- Early intervention and Delayed intervention
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,052 participants
- Where
- 24 sitesFrance
- Study dates
- 17 Dec 2025to 1 Oct 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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; Age > 65 years old.
- 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
Who cannot join
- Patient unable to give informed consent
- Curators, 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
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- Patient with haematological 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
- Patient with Sequential Organ Failure Assessment (qSOFA ) score ≥ 2 at randomization (acute severe febrile illness)
- Patient hospitalized in an Intensive Care Unit
- Pregnancy
- 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.
- S. pneumoniae infection with laboratory confirmation (blood culture, culture from a sterile site, urinary or Cerebrospinal fluid antigens, sputum culture with > 10^7 colony forming unit (CFU)/mL) being the cause of the current hospitalization
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Elisabeth BOTELHO-NEVERS, MD PhD contact
24 sites in 1 country
France24 sites, 24 recruiting
- Not yet recruiting
Centre Hospitalier
Annecy, 74000
JANSSEN CECILE, MD, 450636602 ext. +33, cjanssen@ch-annecygenevois.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Besançon, 25000
KEVIN BOUILLER, MD, (0)3 81 66 81 66 ext. +33, kevin.bouiller@chu-besancon.fr
- Not yet recruiting
Centre Hospitalier
Bordeaux, 33000
CHARLES CAZANAVE, PHD, (0)556795536, charles.cazanave@chu-bordeaux.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Brest, 29609
ROZENN LE BERRE, PHD, (0)298347336 ext. +33, rozenn.leberre@chu-brest.fr
- Not yet recruiting
Centre Hospitalier
Brest, 29609
SYLVAIN JAFFUEL, MD, (0)298347213, sylvain.jaffuel@chu-brest.fr
- Not yet recruiting
Centre Hospitalier General Metropole Savoie
Chambéry, 73011
EMMANUEL FORESTIER, MD, (0)479965172 ext. +33, emmanuel.forestier@ch-metropole-savoie.fr
- Not yet recruiting
Centre Hospitalier de Creteil
Créteil, 94000
ANTOINE FROISSART, MD, (0)157022783 ext. +33, antoine.froissart@chicreteil.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Dijon, 21000
LIONEL PIROTH, PHD, (0)380293305 ext. +33, lionel.piroth@chu-dijon.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Grenoble, 38043
OLIVIER EPAULARD, PHD, (0)476765291 ext. +33, oepaulard@chu-grenoble.fr
- Not yet recruiting
Centre Hospitalier
La Roche-sur-Yon, 85925
THOMAS GUIMARD, MD, (0)251446385, thomas.guimard@ght85.fr
- Not yet recruiting
Centre Hospitalier General
Le Mans, 72000
SOPHIE BLANCHI, MD, (0)2434343 ext. +33, sblanchi@ch-lemans.fr
- Not yet recruiting
Centre Hospitalier
Le Puy-en-Velay, 43000
CYRILLE CORNILLE, MD, (0)4 71 04 32 10 ext. +33, cyrille.cornille@ch-lepuy.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Lille, 59037
KARINE FAURE, PHD, (0)320445743, karine.faure@chu-lille.fr
- Not yet recruiting
Hospices Civils de Lyon
Lyon, 69004
ANNE CONRAD, MD, (0)472071107 ext. +33, anne.conrad@chu-lyon.fr
- Not yet recruiting
Centre Hospitalier Regional Universitaire
Montpellier, 34295
CORRINE MERLE DE BOEVER, MD, (0)467337211 ext. +33, c-merle_de_boever@chu-montpellier.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Nancy, 54511
BENJAMIN LEFEVRE, PHD, (0)383157654 ext. +33, b.lefevre@chru-nancy.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Nantes, 44093
ANNE-SOPHIE LECOMPTE, MD, (0)240083112 ext. +33, annesophie.lecompte@chu-nantes.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Nice, 06202
ELISA DEMONCHY, MD, (0)686778358 ext. +33, demonchy.e@chu-nice.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Nîmes, 30029
PAUL LOUBET, PHD, (0)466684149 ext. +33, paul.loubet@chu-nimes.fr
- Not yet recruiting
Centre Hospitalier Bichat
Paris, 75012
XAVIER LESCURE, PHD, (0)140256994 ext. +33, xavier.lescure@inserm.fr
- Not yet recruiting
Assistance Publique Hopitaux de Paris
Paris, 75679
ODILE LAUNAY, PHD, (0)158412858 ext. +33, odile.launay@aphp.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Rennes, 35000
LEA PICARD, MD, (0)3329928 ext. +33, lea.picard@chu-rennes.fr
- Not yet recruiting
Centre Hospitalier Universitaire
Rouen, 76000
MANUEL ETIENNE, PHD, (0)232888739 ext. +33, manuel.etienne@chu-rouen.fr
- Recruiting
CHU de Saint-Etienne
Saint-Etienne, France, 42055
Elisabeth BOTELHO-NEVERS, MD PhD
About this study
Official title: Immunogenicity and Safety of the 20-Valent Pneumococcal Conjugate Vaccine (PCV-20) Administered During an Acute Febrile Illness in Adults: a Multicentric Randomized Non-inferiority Trial
Streptococcus pneumoniae is responsible for serious infections associated to numerous hospitalizations and high rate of mortality. The incidence and therefore the burden of pneumococcal infections have been significantly reduced thanks to the use of pneumococcal conjugate vaccines (PCVs). PCVs were shown to be effective against vaccine-type serotypes causing both non-invasive and invasive pneumococcal diseases (IPD) in children and adults. PCVs use in children was shown to have an impact on IPD incidence among adults due to herd immunity and on antimicrobial resistance. To increase the protection of at-risk patients against IPD, the 20-valent PCV (PCV-20) is recently recommended in adults, after a period where PCV-13 followed by pneumococcal polysaccharide vaccine 23 valent (PPV-23) was recommended. PCV-20 effectiveness against IPD and against pneumonia was inferred from immunobridging with PCV-13. Indeed PCV-13 was shown effective to reduce the incidence of low respiratory tract infections and IPD (bacteraemia and meningitis) in 65-years-old-adults and older. Currently immunization against S. pneumoniae is recommended with PCV-20 for adult patients at-risk for IPD such as immunocompromised (=high-risk patients) and in immunocompetent people with underlying chronic conditions (cardiovascular, liver, pulmonary, kidney diseases and diabetes mellitus) (=medium risk patients). However, vaccine coverage against IPD in adults remains low globally, and does not exceed 5 % in France. Reducing missed opportunities of vaccination for S. pneumoniae is crucial.
Read the detailed description
Patients at-risk of IPD are very frequently hospitalized for acute febrile illnesses. More than 50 % of the IPD at-risk patients hospitalized for an IPD or a pneumonia have been admitted to the hospital during the past 5 years without receiving a pneumococcal vaccination. Hospitalization appears to be therefore an opportunity to provide vaccines. However, physicians usually consider that vaccines should be postponed during an acute febrile illness including if non-severe. This consideration of not vaccinating during an acute febrile illness is however not evidence-based. This is associated to concerns about a potential risk of an impaired response to the vaccine and safety. In children, data about vaccination during a febrile illness have shown no safety nor efficacy concerns. In most countries, recommendations regarding this particular point are unclear.
In fine, vaccination is then rarely provided during the hospital stay as well as after discharge including in the USA, a country where it is recommended to vaccinate whatever the body temperature is and during hospitalization. Reluctance to immunize adults in this situation is probably due to the absence of evidence showing that it is as effective and safe as vaccinating patients without an acute or febrile illness.
To reduce the number of missed opportunities to immunize adults against S. pneumoniae, investigators aim to demonstrate that the administration of PCV-20 during an acute non-severe febrile illness is non-inferior than the administration one month after fever resolution in terms of immunogenicity (assessed by vaccine types (VT) Immunoglobulin G (IgG) concentrations and at least 2-fold change increase), and that it is as safe.
- Conditions
- Acute Febrile Illness, Pneumococcal Infections
- Being tested
- Early intervention, Delayed intervention
- Keywords
- vaccin, pneumococcal, Prevenar 20, Acute febrile illness, infections, PCV-20, PCV-21
- Medical subject headings
- Pneumococcal Infections, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early interventionBiological
In this arm, patient will receive unique dose of the PCV-20 vaccine (Prevnar 20) as soon as possible and until 72h after apyrexia.
The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.
Delayed interventionBiological
In this arm, from 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature < 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive unique dose of the PCV-20 vaccine (Prevnar 20).
The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.
| Study group | Role | What they receive |
|---|---|---|
| Early vaccination | Experimental | The patient will receive unique dose of the PCV-20 vaccine as soon as possible and until 72h after apyrexia.
The "Prevenar 20" will be used Receives: Biological: Early intervention |
| Delayed vaccination | Active comparator | From 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature < 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive PCV-20 vaccination The "Prevenar 20" will be used Receives: Biological: Delayed intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of immune "good responders" to PCV-20 in both arms
Good responders is defined as - 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.
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.
Measured: 1 month post vaccination
Secondary outcomes (13)
Safety endpoints in both arms in the month following vaccination : adverse events
Number, type and severity of solicited (in the 7 days following vaccination) and unsolicited (in the month following vaccination) adverse events
Measured: 1 month post vaccination
Frequency of local reactions
Local reactions will be defined as : pain, redness, and swelling at the study vaccine injection site and limitation of arm movement
Measured: 1 month post vaccination
Frequency of systemic events related to the vaccination
Onset or worsening of fever, diarrhoea, chills, fatigue, headache, vomiting, decreased appetite, rash, muscle pain, joint pain). An independent blinded central adjudication committee will define the onset or worsening of symptoms and will review all systemic events.
Measured: 1 month post vaccination
Proportion of immune good responders serotype by serotype
"Good responders" being defined above (primary end-point)
A blood sample for immunologic analysis will be performed
Measured: 1 month post vaccination
opsonophagocytic activity (OPA) IgG titers for serotype by serotype
A blood sample for immunologic analysis will be performed. ELISA method will be used for immunologic analysis.
Measured: 1 month post vaccination
Proportion of the participants immune "good responders" to PCV-20 in both arms.
"Good responders" being defined above (primary end-point) A blood sample for immunologic analysis will be performed. ELISA method will be used for immunologic analysis.
Measured: 1 year post vaccination
Number of low respiratory tract infections events
Data about occurrence of respiratory infections will be recorded.
Measured: 1 year post vaccination
Number of confirmed S.pneumoniae infections
Data about pneumococcal infection will be recorded.
Measured: 1 year post vaccination
Analyze the gut microbiota on the immune response
Analyze the gut microbiota on the immune response in both arm ( during an acute febrile illness or 15-58 days after resolution of the acute febrile illness)
A stool sample is taken before vaccination
Measured: 1 year post vaccination
Reactogenic inflammatory response after vaccination
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.
Measured: 1 month post vaccination
Frequency of specific PCV-20 interferon-gamma (IFNg) secreting CD4 or CD8 T cells
Blood sample will be collected 1 month post-vaccination.
Measured: 1 month post vaccination
Frequency of specific PCV-20 IFNg secreting CD4 or CD8 T cells
Blood sample will be collected 1 year post-vaccination.
Measured: 1 year post vaccination
Proportion of volunteers with circulatory immunoglobulin A (IgA)
Blood sample will be collected 1 month post-vaccination.
Measured: 1 month post vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2025
- Study start17 Dec 2025
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Febrile IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective Randomised Open Blinded End-point trial (PROBE) Non inferiority design
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,052 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Saint Etienne
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France, IREIVAC/COVIREIVAC Network
- Responsible party
- Sponsor
- Investigators
- Elisabeth BOTELHO-NEVERS, MD PhD, Principal investigator, Centre Hospitalier Universitaire de Saint Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06822907
- Sponsor's protocol ID
- 19PH225
- Other IDs
- 2024-517411-73-00
- Acronym
- PREV-HOSPIT
- Status last verified
- Mar 2026
- First submitted
- 7 Feb 2025
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No