Lactoferrin in Covid-19 Hospitalized Patients

NCT ID: NCT04847791

Last Updated: 2021-04-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-14
• Study Completion Date: 2022-12-31

Brief Summary

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.

Detailed 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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group A

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

Group Type: EXPERIMENTAL

Bovine lactoferrin

Intervention Type: DIETARY_SUPPLEMENT

Oral Administration of Bovine Lactoferrin -fixed dose 800 mg / day for 30 days

Group B

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.

Group Type: PLACEBO_COMPARATOR

Placebo administration

Intervention Type: DIETARY_SUPPLEMENT

capsule identical with the same amount as an inert compound, starch of corn powder), according to the same pattern of use.

Interventions

Bovine lactoferrin

Oral Administration of Bovine Lactoferrin -fixed dose 800 mg / day for 30 days

Intervention Type: DIETARY_SUPPLEMENT

Placebo administration

capsule identical with the same amount as an inert compound, starch of corn powder), according to the same pattern of use.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

MOSIAC

Eligibility Criteria

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

4. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Paolo Manzoni

OTHER

Sponsor Role: lead

Responsible Party

Paolo Manzoni Study Group

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paolo Manzoni, MD

Role: PRINCIPAL_INVESTIGATOR

ASL BI

Locations

ASL BI Ospedale degli Infermi

Ponderano, Biella, Italy

Site Status: RECRUITING

AOU Ospedale Maggiore della Carità

Novara, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Paolo Manzoni, MD

Role: CONTACT

paolomanzoni@hotmail.com

00390151515 ext. 7626

Facility Contacts

Paolo Manzoni, MD

Role: primary

paolomanzoni@hotmail.com

0151515 ext. 7626

Pier Paolo Sainaghi, MD

Role: primary

References

Andersen JH, Jenssen H, Sandvik K, Gutteberg TJ. Anti-HSV activity of lactoferrin and lactoferricin is dependent on the presence of heparan sulphate at the cell surface. J Med Virol. 2004 Oct;74(2):262-71. doi: 10.1002/jmv.20171.

Reference Type: BACKGROUND

PMID: 15332275 (View on PubMed)

Avula A, Nalleballe K, Narula N, Sapozhnikov S, Dandu V, Toom S, Glaser A, Elsayegh D. COVID-19 presenting as stroke. Brain Behav Immun. 2020 Jul;87:115-119. doi: 10.1016/j.bbi.2020.04.077. Epub 2020 Apr 28.

Reference Type: BACKGROUND

PMID: 32360439 (View on PubMed)

Yang Z, Jiang R, Chen Q, Wang J, Duan Y, Pang X, Jiang S, Bi Y, Zhang H, Lonnerdal B, Lai J, Yin S. Concentration of Lactoferrin in Human Milk and Its Variation during Lactation in Different Chinese Populations. Nutrients. 2018 Sep 5;10(9):1235. doi: 10.3390/nu10091235.

Reference Type: BACKGROUND

PMID: 30189612 (View on PubMed)

Wang Y, Wang P, Wang H, Luo Y, Wan L, Jiang M, Chu Y. Lactoferrin for the treatment of COVID-19 (Review). Exp Ther Med. 2020 Dec;20(6):272. doi: 10.3892/etm.2020.9402. Epub 2020 Oct 27.

Reference Type: BACKGROUND

PMID: 33199997 (View on PubMed)

Wakabayashi H, Oda H, Yamauchi K, Abe F. Lactoferrin for prevention of common viral infections. J Infect Chemother. 2014 Nov;20(11):666-71. doi: 10.1016/j.jiac.2014.08.003. Epub 2014 Aug 30.

Reference Type: BACKGROUND

PMID: 25182867 (View on PubMed)

Other Identifiers

2020/279

Identifier Type: -

Identifier Source: org_study_id