Clinical trial NCT04844658: Covid-19, Hospitalized, PatIents, Nasafytol
Official title: A Comparative Randomized Clinical Study on Covid-19 Positive Hospitalized Patients Supplemented With NASAFYTOL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronavirus Infection
Lead sponsor: Tilman S.A.
Sponsor class: INDUSTRY
Collaborators: name: Artialis
First posted: 2021-04-14
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The objective of this study is to evaluate the effect and safety of NASAFYTOL® on COVID-19 positive hospitalized patients as a supportive supplementation to standard-of-care in improving clinical parameters safely during hospital admission (maximum 14 days).

The study is a standard-of-care comparative, open, parallel two-arms and randomized trial in 50 adult patients positive to COVID-19 infection and hospitalized. It will be monocentric but may be extended to several investigation sites (multicentric) depending on the evolution of the epidemic within the hospitals.

Detailed description: 50 patients (25 per arm) infected with COVID-19 and hospitalized (depending on the progress of the pandemic and therefore the presence of COVID-19 patients, this number could reach 100 (50 per arm)). The first ten sentinel patients will be monitored at the safety level before enrolling the rest of the participants.

The effect and safety of NASAFYTOL® will be evaluated using the following outcome measures:

1. Improvement of clinical condition of the patient defined by the COVID-19 WHO ordinal Outcomes score. This scale reflects a range from uninfected to dead, where 0 is "no clinical or virological evidence of infection", 1 is "no limitation of activities", 2 is "limitation of activities", 3 is "hospitalized, no oxygen therapy", 4 is "oxygen by mask or nasal prongs", 5 is "non-invasive ventilation or high-flow oxygen", 6 is "intubation and mechanical ventilation", 7 is "ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)", and 8 is "death".

   * Time to a 1-point decrease
   * Score at 14 days (or at hospital leave if \<14 days) post randomization
2. Duration (days) of hospitalization
3. In-hospital mortality
4. Temperature (fever):

   * Time to resolution of fever for at least 48 hours without antipyretics for 48 hours - Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic)
   * Proportion of participants with normalization at day 14 (or at hospital leave if \<14 days)
5. Need of oxygen therapy
6. Tolerance as defined by the Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)
7. Compliance using the pill count
8. Blood test:

   * C-reactive proteins : Time to halving of (or achieve normal ) CRP levels compared to peak value during trial
   * Hematological values (included Lymphocyte Count) and others routine laboratory parameters (LDH, albumin, etc.): Time to normalization
   * Vitamin D serum concentration: comparison of concentration between inclusion and end of trial and between the 2 arms.

   Optional outcome measures will be perform if data is available from routine practice:
9. Blood tests between inclusion and end of trial
10. Radiological response - Thoracic CT scan or Chest XR
11. Oxygenation PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) :

    * Time to improvement (TBD) in oxygenation for at least 48 hours
    * Proportion of participants with normalization at day 14 (or at hospital leave if \<14 days)
12. Time until negative RT-PCR

Eligibility criteria: Inclusion Criteria:

* Adult ≥ 18 years of age at the time of inclusion in the study;
* Recently hospitalized patients in whom SARS CoV-2 infection has been laboratory confirmed by RT-PCR or other commercial or public health test on any sample.
* Severity of 3-4-5 according to the WHO 7-point ordinal scale (3: hospitalized, no oxygen therapy; 4: hospitalized, oxygen by mask or nasal prongs; 5:non-invasive ventilation or high-flow oxygen);
* Subject (or authorized legal representative) who can provide oral or written informed consent before beginning any study procedure;
* Understand and agree to abide by the study procedures.

Exclusion Criteria:

* Contra-indication to NASAFYTOL® or constituents (incl. Vit D): hypersensitivity or allergy to product components;
* Swallowing disorder or inability to take oral caps;
* Presence of comorbidities that imply a poor prognosis (according to clinical judgment);
* Pregnancy or breastfeeding women; If patient is a female of childbearing potential, patient must use an effective means of birth control (oral, intravaginal or transdermal oestrogen-progestogen combined hormonal contraceptives or intrauterine devices or sexual abstinence);
* Serious or active bacterial infections or documented sepsis by pathogens other than SARS-CoV-2;
* Patients participating in clinical trials of other products; Patients presenting acute impairment of renal function or nephrolithiasis; ALT/AST\> 5 times the normal limit, or Neutropenia (Absolute neutrophil count \< 500/uL), or Thrombocytopenia (Platelets \< 50,000/uL).

Primary outcomes:
measure: Improvement of the patient's clinical condition based on the WHO ordinal outcomes score
timeFrame: day 14
measure: Improvement of the patient's clinical condition based on the WHO ordinal outcomes score
timeFrame: day 14
measure: Duration of hospitalization
timeFrame: day 14
measure: In-hospital mortality
timeFrame: day 14
measure: Temperature (fever)
timeFrame: day 14
measure: Temperature (fever)
timeFrame: day 14
measure: Need of oxygen therapy
timeFrame: day 14
measure: Tolerance as defined by the Incidence of Adverse Events (AE)
timeFrame: day 14
measure: Tolerance as defined by the incident of Serious Adverse Events (SAE)
timeFrame: day 14
measure: Compliance using the pill count
timeFrame: day 14
measure: Blood test
timeFrame: day 14
measure: Blood test
timeFrame: day 14
measure: Blood test
timeFrame: day 14
Secondary outcomes:
Other outcomes:
measure: Radiological response (exploratory)
timeFrame: day 14
measure: Oxygenation
timeFrame: day 14
measure: Oxygenation
timeFrame: day 14
Locations:
city: Brussels
country: Belgium
facility: Delta Hospital
Study officials:
References: