Clinical trial NCT04836260: Preemptive Use of Convalescent Plasma for High-risk Patients With COVID-19
Official title: Preemptive Use of Convalescent Plasma for High-risk Patients With SARS-CoV-2 Infection: Phase III-IV Non-controlled Non-randomised Swiss Multicentric Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Covid19
Immuno-Deficiency
Old Age; Debility
Keywords: SARS-CoV-2
Convalescent plasma
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: University Hospital, Basel, Switzerland
name: Ospedale Regionale di Lugano
name: Hôpital Fribourgeois
First posted: 2021-04-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: open-label non-controlled, non-randomised interventional study
Primary purpose: PREVENTION

Brief summary: Convalescent plasma therapy has been recognized as safe and plasma transfusion is routinely used in clinical practice. A recent study showed that early administration of convalescent plasma can decrease the risk of complications in specific high-risk population.

The aim of the present study is to offer convalescent plasma therapy to immunocompromised patients and older adults in the early phase of a SARS-Cov-2 infection in order to accelerate viral clearance and prevent complication

Detailed description: This is an open-label non-controlled, non-randomised interventional study. Study population consist in immunocompromised patients and older adults with or without co-morbidities.

Included patients will receive at least one unit of convalescent plasma with NTAB titer ≥1:160 or equivalent at maximum 3-7 days after diagnosis by RT-PCR or symptom onset or if having mild-moderate disease (WHO scale \<4).

Patients will be followed-up up to 28 days to assess progression to WHO scale 4 disease, and 28-days mortality and viral load kinetics.

Eligibility criteria: Inclusion Criteria:

1. Immunocompromised patients defined as

   1. Solid organ transplant ≤1 year before inclusion or treated for acute or chronic rejection episode or
   2. Allogeneic stem cell transplant recipients ≤2 years before inclusion or treated for acute GvHD ≥grade 2 or chronic moderate-severe GvHD or
   3. Active solid or haematological oncological disease with curative perspectives or
   4. HIV infection with CD4\<350 or
   5. Hypogammaglobulinemia and other severe genetic immunological defect or
   6. Auto-immune disease with biological immunosuppressive treatment\* or
   7. Other significant immunosuppressive condition such as IgG \<6, treamtent with Rituximab or other biological lymphopenic treatment AND

      * Age ≥ 18 years old and
      * 2 distinct ABO group determination and
      * Positive RT-PCR for SARS-CoV-2 on a respiratory tract sample of ≤ 7 days and days post symptom onset (DPOS) ≤ 7 days at inclusion and/or
      * No oxygen requirement (WHO 8 ordinal scale \< 4): asymptomatic, mild or moderate disease, or O2 saturation ≥ 90% at room temperature and
      * Compatible ABO donor with neutralizing antibodies (NTAB) ≥1 :160 or equivalent according to predefined antibody commercial assays cut-offs (see Study procedures)
      * RT-PCR on a respiratory tract sample with CT value\<20 or ascending kinetics at the time of infusion (highly suggested but not necessary)
2. Older adults defined as Age ≥ 75 years old or ≥ 65 years old with at least one co-existing condition

   * Arterial hypertension under pharmacological treatment
   * Diabetes in treatment
   * Obesity (BMI ≥ 30 kg/m2)
   * Chronic obstructive pulmonary disease stade GOLD ≥2
   * Respiratory insufficiency due to any pneumopathy or neurologic disease.
   * Cardiovascular disease as defined by either known coronary heart disease, history of ischemic or hemorrhagic stroke or cardiac insufficiency (ejection fraction \<40%)
   * Chronic kidney disease (GFR\<60 ml/min) AND
   * 2 distinct ABO group determination and
   * Positive RT-PCR for SARS-CoV-2 on a respiratory tract sample of ≤ 3 days and days post symptom onset (DPOS) ≤ 3 days at inclusion or RT-PCR on a respiratory tract sample with CT value\<20 or ascending kinetics at the time of perfusion and
   * No additional oxygen requirement compared to baseline (WHO 8 ordinal scale \< 4): asymptomatic, mild or moderate disease and
   * Compatible ABO donor with neutralizing antibodies (NTAB) ≥1 :160 or equivalent according to predefined antibody commercial assays cut-offs (see Study procedures)

Exclusion criteria:

Seroconversion at the time of inclusion

* Palliative care
* No signed informed consent
* History of previous transfusion-related Grade 3 adverse event according to Swissmedic definitions
* Disseminated intravascular coagulopathy (depending on specialist evaluation)
* Uncontrolled acute hypervolemia

Primary outcomes:
measure: Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement)
timeFrame: 7 days after plasma infusion
measure: Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement)
timeFrame: 14 days after plasma infusion
measure: Proportion of death
timeFrame: 28 days after plasma infusion
Secondary outcomes:
measure: Proportion of patients with cleared nasopharyngeal viral load
timeFrame: 7 days after plasma infusion
measure: Proportion of patients with cleared nasopharyngeal viral load
timeFrame: 14 days after plasma infusion
Other outcomes:
measure: Proportion of patients that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement)
timeFrame: 21 days after plasma infusion
measure: Proportion of patients with cleared nasopharyngeal viral load
timeFrame: 21 days after plasma infusion
Locations:
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Fribourg
country: Switzerland
facility: HFR-Fribourg Hôpital Cantonal
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
Study officials:
affiliation: University Hospital, Geneva
name: Laurent Kaiser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Regionale di Lugano
name: Enos Bernasconi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HFR-Fribourg Hôpital Cantonal
name: Véronique Erard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinik Infektiologie & Spitalhygiene
name: Maja Weisser, MD
role: PRINCIPAL_INVESTIGATOR
References: