Clinical trial NCT04405271: TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)
Official title: Randomized, Double-blind, Placebo-controlled Trial of TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Healthcare Workers
COVID-19
SARS-CoV 2
Keywords: SARS Virus, SARS-CoV-2, COVID-19, Health Personnel
Lead sponsor: Hospital Italiano de Buenos Aires
Sponsor class: OTHER
Collaborators: name: Sociedad Argentina de Infectología (SADI) (Argentine Society of Infectious Diseases)
First posted: 2020-05-28
Enrollment: 1378
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized (1:1), double-blind, placebo-controlled clinical trial
Primary purpose: PREVENTION

Brief summary: A randomized parallel double-blinded placebo-controlled clinical trial to evaluate the effect of Emtricitabine/Tenofovir alafenamide (FTC/TAF) compared with placebo on the risk of developing SARS-CoV-2 disease (COVID-19) in healthcare workers with high transmission risk in addition to currently recommended control measures.

Detailed description: Randomized, double-blind, placebo-controlled clinical trial. Phase III clinical trial for a new indication

Rationale One of the most affected subgroups during the current pandemic is represented by healthcare workers. In Argentina between 14 and 17% of the total COVID-19 cases are represented by this subgroup. In this sense, it appears as an adequate strategy testing the efficacy of pharmacological PrEP approaches on top of the currently recommended control measures.

The use of placebo is warranted for two main reasons: all healthcare workers will be allowed and encouraged to comply with non-pharmacological infection control measures for the protection of viral transmission. On the other hand, the use of a blinded placebo is intended for avoiding relaxation of the non-pharmacological control measures.

Tenofovir has been identified by both docking and in vitro studies as an inhibitor of RdRp (RNA dependent RNA polymerase) of coronavirus.

FTC/TAF has the additional advantage that is already being used in a pre-exposure prophylaxis setting and its safety is widely known.

Main objective To evaluate the risk of developing SARS-CoV-2 disease (COVID-19) in healthcare workers with high transmission risk in addition to currently recommended control measures.

Eligibility criteria: Inclusion Criteria:

1. Healthcare workers voluntarily deciding to participate in the study
2. Understanding the study purpose
3. Having between 18 and 70 years old
4. Having a high transmission risk for Covid-19. Physicians, nurses, lab technicians, physical therapists, or cleaning personnel working at COVID-19 areas, hospital emergency areas, or Intensive care units from healthcare institutions with the direct assistance of patients with Covid-19.
5. Not having a prior diagnosis of SARS-CoV-2 infection (COVID-19)
6. Having a negative IgM/IgG antibodies test for SARS-CoV-2 (COVID-19) prior to study entry
7. Negative pregnancy test for childbearing age women within 7 days prior to study entry.
8. Childbearing age males and females should comply with the use of a proven contraceptive method (double barrier methods, oral contraceptives or contraceptive hormone implants) during the course of the study and at least one month after study completion.

Exclusion Criteria:

1. Having symptoms compatible with COVID-19
2. Diagnosed HIV infection
3. Current use of Pre-exposure prophylaxis for HIV
4. Diagnosed Hepatitis B infection.
5. Diagnosed renal insufficiency and or current hemodialysis need
6. Diagnosed osteoporosis under pharmacological treatment.
7. Weight \< 40kg
8. Current immunosuppressive or serious hematological condition
9. Prior use of pre-exposure prophylaxis for SARS-CoV-2
10. Current pregnancy or pregnancy plan within the study course.
11. Current breastfeeding
12. Known hypersensitivity to any of the study medication components.

Primary outcomes:
measure: COVID-19 incident cases
timeFrame: During treatment (12 weeks)
Secondary outcomes:
measure: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology
timeFrame: During treatment (12 weeks)
measure: Severity of symptomatic COVID-19
timeFrame: During treatment (12 weeks)
measure: Respiratory symptom duration in days
timeFrame: During treatment (12 weeks)
measure: Relation between treatments and symptoms duration
timeFrame: During treatment (12 weeks)
measure: Time course of specific IgM/IgG seroconversion
timeFrame: During treatment (12 weeks)
Other outcomes:
Locations:
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Sociedad Argentina de Infectología, A. J. Carranza 974
state: Capital Federal
Study officials:
affiliation: Hospital Italiano de Buenos Aires
name: Waldo H Belloso, MD
role: STUDY_CHAIR
affiliation: HIBA
name: Ventura Simonovich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sanatorio Britanico
name: Esteban Nannini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Austral
name: Wanda Cornistein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Richmond Laboratorio
name: Marcelo Figueiras, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Richmond Laboratorio
name: Elvira Zini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sanatorio Allende (Córdoba)
name: Fernando Riera, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HUESPED
name: Omar Sued, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Italiano de La Plata
name: Santiago Ramirez Borga, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Padilla (Tucumán)
name: Gustavo Costilla Campero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Bernardo Houssay
name: Gustavo D Lopardo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Alende (Mar del Plata)
name: Gonzalo Corral, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci. 2020 May 1;248:117477. doi: 10.1016/j.lfs.2020.117477. Epub 2020 Feb 28.
citation: Castillo-Mancilla JR, Meditz A, Wilson C, Zheng JH, Palmer BE, Lee EJ, Gardner EM, Seifert S, Kerr B, Bushman LR, MaWhinney S, Anderson PL. Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals. J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):495-501. doi: 10.1097/QAI.0000000000000529.