Lactoferrin in Covid-19 Hospitalized Patients (LAC)

Paolo Manzoni

Status: Unknown

Conditions: Covid19

Treatments: Dietary Supplement: Bovine lactoferrin; Dietary Supplement: Placebo administration

Study type: Interventional

Funder types: Other

Identifiers

NCT04847791

2020/279

Details and patient eligibility

About

TRIAL LAC is a randomized double-blind non profit multicenter study with a nutritional product: bovine lactoferrin - Mosiac 200 mg.

the hypothesis to be confirmed is that bovine LF, administered daily orally in addition to standard therapies for 1 month to hospitalized patients with Covid-19 infection, can be useful to limit the severity, progression of the disease, shorten the time of swabs negativization (i.e. time required to eliminate the virus) and to reduce the morbidity load associated with it.

Patient recruitment will involve 2 centers in Italy: Ospedale degli Infermi (Ponderano, Biella) and AOU Maggiore della Carità (Novara).

The subjects enrolled will be randomized to two Groups:

Group A (experimental arm) - Standard Anti-Covid-19 Therapy + Oral Administration of Bovine Lactoferrin (fixed dose 800 mg / day) for 30 days Group B (control arm) - Standard anti-Covid-19 therapy + Placebo administration (identical capsule with the same amount as an inert compound, starch of corn powder), according to the same pattern of use.

It should be specified that the study treatment and placebo will be administered in addition to the standard care in place, and therefore in addition to all the pharmacological treatments currently used in clinical hospital practice against Covid-19.

Full description

It has been shown with 'in vitro' studies that LF is able to prevent the entry of SARS-CoV-2 into the of the host cells.

Overall, the available evidence suggests that LF may be a therapeutic option that can be used to counteract and reduce the severity of Covid 19 infection. The study hase been designed in order to demonstrate efficacy of Lactoferrin in vivo.

Patients who will be admitted by Participating Centers for Covid-19 Infection will be screened for eligibility for study . If considered eligible, they will be offered participation in the Study, and it will be proposed and informed consent will be explained. Eligible patients will be registered in a centralized database at the IT systems of the University of Piedmont Orientale (UPO)/Hospital-University Company "Maggiore della Carità" of Novara. The pseudo-anonymized patient data will be recorded by the clinical centre in an 'ad hoc' Clinical Report Form with web-based access.

After obtaining informed consent, patients will then be randomised to LF or placebo group allocation using previous randomization lists Prepared. Randomization will take place on a competitive and balanced basis per clinical center participant. Permuted block randomization of size 4 will be implemented with an allocation ratio of 1:1 to ensure the balance between the groups of treatment. The randomization list will be managed through a REDCap randomization module.

The Hospital Pharmacy of the Participating Center, not involved in the enlistment of patients, will prepare a numbered sequence of sealed envelopes containing the code of allocation, and will keep its list that will remain inaccessible to the professionals involved in recruitment.These sealed envelopes will be opened sequentially, at the time of randomization.

The maintenance of the blind person will be guaranteed by keeping the staff randomization lists, i.e. the staff of the Hospital Pharmacy, on the one hand (staff who will also manage and deliver to the investigators the products being studied, which will look the same), and the randomizing and experimenting medical staff, on the other.

The logistical location of the two staff will also be completely separated, in sectors of the Hospital different and distant from each other, and not communicating in any way.

It should be pointed out that the patient enrolled by the clinical centers on the basis of the selection criteria can start standard-of-care therapy, in any case, before the randomization procedure being the identical basic therapeutic regimen in the two study arms.

For the calculation of the sample size required to demonstrate the primary endpoint, it was used a model built on historical data regarding the same endpoint. Pre-trial data from the two Participating Centres estimate the need for ICU admission at 25%; the need for mechanical ventilation in 30%; hospital mortality in 15%; the average duration hospitalization in 16 days.

The sample size was determined considering a two-sided t-test for two independent samples according to the following parameters:

1. A correct alpha level of 0.025 for two Bonferroni-method endpoints (Alpha total=0.025x2=0.05)
2. A total power of 0.8
3. A Cohen h effect size of 0.44 (corresponding to an effect standardized medium/small [Cohen 1977]), i.e. with a 14-day resignation rate of 60% for controls and 80% for treaties.

In this scenario, the size of the study achieved consists of 97 patients per arm of study. Calculations were performed using the R 3.6.1 software [Core Team 2015] and the pwr package [Champely 2018]. references:

• Cohen, J. Statistical power analysis for the behavioral sciences (rev.ed.1977).
• Core Team R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2015;
• Champely, S.; Ekstrom, C.; Dalgaard, P.; Gill, J.; Weibelzahl, S.; Anandkumar, A.;Ford, C.; Volcic, R.; De Rosario, H.; De Rosario, M.H. Package 'pwr.' R package version 2018, 1-2.

Enrollment: 194 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Hospitalization in non-ICU ward for Covid-19 infection, with virological diagnosis SARS-CoV2 confirmed via RT-PCR (or quick test)
2. Age>18 aa
3. Covid symptomatology story from no more than 12 days

Exclusion criteria

1. Refusal of consent

2. Need for immediate admission to intensive care

3. Severe neoplasms (in advanced stage)

4. Allergies or intolerances known to Lactoferrin

5. Already being treated with Lactoferrin at the entrance to the Hospital 5. Patients with end-stage renal failure (stage 5) 6. Extremely serious general conditions to suggest an imminent exitus 7. Clinical conditions of absolute impossibility of tolerating ingestion of drugs/capsules due to conditions contraining the initiation of therapy for os.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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194 participants in 2 patient groups, including a placebo group

Group A

Experimental group

Description:

Standard Anti-Covid-19 Therapy + Oral Administration of Bovine Lactoferrin 400mg (two capsules of Mosiac 200 product) every 12 h (i.e., fixed dose 800 mg / day) for 30 days and still away from meals

Treatment:

Dietary Supplement: Bovine lactoferrin

Group B

Placebo Comparator group

Description:

Standard anti-Covid-19 therapy + Placebo administration (capsule identical with the same amount as an inert compound, starch of corn powder), according to the same pattern of use.

Treatment:

Dietary Supplement: Placebo administration