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. 2020 Jul 10;2020(7):CD013600. doi: 10.1002/14651858.CD013600.pub2

NCT04366245.

Study name Phase I / II multicentre, randomized and controlled clinical trial to evaluate the efficacy of treatment with hyperimmune plasma obtained from convalescent antibodies of COVID‐19 infection
Methods

  • Trial design: phase I/II RCT, open‐label, parallel assignment

  • Sample size: e.g. 36 in each arm (72)

  • Setting: e.g. inpatient

  • Country: Spain

  • Language: English

  • Number of centres: NR


Inclusion criteria:

  • Informed consent prior to performing procedures. Oral consent accepted to prevent paper handling.

  • Patients of both sexes, and ≥ 18 years

  • SARS‐CoV‐2 infection determined by PCR in a sample of naso‐oropharyngeal exudate or other respiratory specimen or determination of specific positive IgM antibodies, in < 72 h before randomisation.

  • Patients requiring hospitalisation for pneumonia COVID‐19 without need until randomisation of mechanical ventilation (invasive or non‐invasive), and at least one of the following:

    • O2 saturation ≤ 94% in ambient air, or PaO2/FiO2 ≤ 300 mm Hg

    • Age > 65 years

    • Presence of: high blood pressure, chronic heart failure, COPD, liver cirrhosis, or other chronic pulmonary and cardiovascular diseases, diabetes, or obesity
Participants

  • Inclusion criteria:

    • All sexes

    • ≥ 18 years

    • Informed consent prior to performing procedures. Oral consent accepted to prevent paper handling.

    • SARS‐CoV‐2 infection determined by PCR in a sample of naso‐oropharyngeal exudate or other respiratory specimen or determination of specific positive IgM antibodies, in < 72 h before randomisation.

    • Patients requiring hospitalisation for pneumonia COVID‐19 without need until randomisation of mechanical ventilation (invasive or non‐invasive), and at least one of the following:

      • O2 saturation ≤ 94% in ambient air, or PaO2/FiO2 ≤ 300 mm Hg

      • Age > 65 years

      • Presence of: high blood pressure, chronic heart failure, COPD, liver cirrhosis, or other chronic pulmonary and cardiovascular diseases, diabetes, or obesity

  • Exclusion criteria:

    • Requirement before randomisation of mechanical ventilation (invasive or non‐invasive)

    • Any of the following analytical data before randomisation: IL‐6 > 80 pg/mL, D‐dimer > 10 times ULN, ferritin > 1000 ng/mL

    • Participation in another clinical trial or experimental treatment for COVID‐19

    • In the opinion of the clinical team, progression to death or mechanical ventilation is highly probable within 24 h, regardless of treatment provision

    • Incompatibility or allergy to the administration of human plasma

    • Severe chronic kidney disease grade 4 or requiring dialysis (ie eGFR < 30)

    • Pregnant, lactating, or fertile women who are not using an effective method of contraception. (Women of childbearing age considered to be all women from 18 years and up to a year after the last menstrual period in the case of menopausal women)
Interventions

  • Intervention(s): COVID‐19 hyperimmune  CP 

  • Details of CP:

    • Type of plasma: NR

    • Volume: NR

    • Number of doses: NR

    • Antibody‐titre: NR

    • Pathogen inactivated: NR

  • Treatment details, including time of plasma therapy (e.g. early stage of disease): before mechanical ventilation is required

  • Comparator: e.g.. conventional treatment

  • Concomitant therapy: hydroxychloroquine + azithromycin or lopinavir/ritonavir + interferon β‐1b + hydroxychloroquine

  • Treatment cross‐overs: no
Outcomes

  • Primary study outcome(s): 

    • Safety: incidence of AEs and SAEs grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE). (time frame: 30 days after enrolment). 

    • Efficacy: death from any cause (time frame: day +21 after randomisation)

    • Efficacy: need for mechanical ventilation (time frame: Day +21 after randomisation)

    • Efficacy: any of the following analytical data after 72 h of randomisation. (time frame: Day +21 after randomisation). IL‐6 > 40 pg/mL, D‐dimer > 1500, ferritin > 1000 ng/mL

    • Efficacy: SOFA scale ≥ 3 after 72 h of randomisation. (time frame: Day +21 after randomisation).

  • Primary review outcomes reported

    • All‐cause mortality at hospital discharge: yes

      • Death from any cause (time frame: Day +21 after randomisation)

      • Mortality on days 14 and 28 (time frame: Days 14 and 28)

    • Time to death: NR

  • Secondary review outcomes reported

    • Number of participants with grade 3 and grade 4 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): yes

      • Incidence of AEs and SAEs grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE). (time frame: 30 days after enrolment)

    • Number of participants with SAEs: yes

      • Incidence of AEs and SAEs grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE)

    • Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8 ‐15 days; 16 to 30 days: yes

      • Need for mechanical ventilation (time frame: Day +21 after randomisation)

    • 30‐day and 90‐day mortality: no

    • Admission on ICU: yes

      • Proportion of participants who required mechanical ventilation (time frame: Until day 28)

    • Length of stay on the ICU: no

    • Time to discharge from hospital: yes

      • Duration of hospitalisation (days) (time frame: until day 21)

  • Additional outcomes

    • Proportion of participants who develop analytical alterations. (time frame: Day +21 after randomisation.). IL‐6 > 40 pg/mL, D‐dimer > 1500, ferritin > 1000 ng/mL until the cure test

    • Cure / clinical improvement (disappearance or improvement of signs and symptoms of COVID‐19) in the cure test. (time frame: Day +21 after randomisation)

    • PCR‐negative for SARS‐CoV‐2 (time frame: on days 7, 14 and 21)

    • Proportion of participants who required treatment with tocilizumab (time frame: until day 21)

    • Virology and immunological variables: qualitative PCR for SARS‐CoV‐2 in naso‐oropharyngeal exudate sample (time frame: at baseline and on day 14)

    • Virology and immunological variables: total antibody quantification (time frame: at baseline and on days 3, 7, 10 (while hospitalisation lasts), and on days 14 and 28 (if able to return to the clinic or are still hospitalised)

    • Virology and immunological variables: quantification of total antibodies in PC donors recovered from COVID‐19 (time frame: before infusion)
Starting date 23 April 2020
Contact information Ana Cardesa Gil 697 95 69 41 ext 0034
ana.cardesa@juntadeandalucia.es
Hospital Unversitario Virgen Macarena, Sevilla, Spain, 41009
Notes

  • Recruitment status: recruiting

  • Prospective completion date: December 2021

  • Sponsor/funding: Andalusian Network for Design and Translation of Advanced Therapies