Randomized, Controlled, Double-blind Clinical Trial Comparing the Efficacy and Safety of Chemoprophylaxis With Hydroxychloroquine in Patients Under Biological Treatment and / or JAK Inhibitors in the Prevention of SARS-CoV-2 Infection

Study Overview
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Brief Summary
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The investigators plan to evaluate a strategy of chemoprophylaxis with hydroxyloquine (HCQ) against COVID-19 infection in patients diagnosed with an immunomediated inflammatory disease who are following a treatment with biological agents and / or Jak inhibitors. The strategy will be carried out through a randomised double blind, placebo-controlled clinical trial and will assess comparative rates of infection (prevalence, incidence), severity including mortality, impact on clínical course of the primary diseases and toxicity. Such evaluation will require prospective surveillance to assess the different end-points. Drug interventions in this protocol will follow the Spanish law about off-label use of medicines.

Official Title
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Randomized, Controlled, Double-blind Clinical Trial Comparing the Efficacy and Safety of Chemoprophylaxis With Hydroxychloroquine in Patients Under Biological Treatment and / or JAK Inhibitors in the Prevention of SARS-CoV-2 Infection

Conditions
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COVID 19, Immunomediated Inflammatory Disease in Treatment With Biological Agents and / or Jak Inhibitors

Intervention / Treatment
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* Drug: Hidroxicloroquina
* Drug: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet the requirements of the New Coronavirus Infection Diagnosis (Acute respiratory infection symptoms or acute cough alone and positive PCR) Aged ≥18 and < 75 years male or female; In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study. Willing to take study medication Willing to comply with all study procedures, Diagnosis of IBD disease, rheumatoid arthritis, seronegative spondyloarthritis or psoriasis for more than 6 months. Be on stable treatment with biological agents, for a minimum period of 6 months, including treatment with Infliximab, etanercept, adalimumab, certolizumab, golimumab, rituximab, abatacept, tocilizumab, sarilumab, secukinumab, vedolizumab, natalizumab, ustekinumab, tofacit Able to provide oral and written informed consent Exclusion Criteria Previous infection with SARS-CoV-2. Current treatment with hydroxychloroquine / chloroquine. Previous or current treatment with tamoxifen or raloxifene. Previous eye disease, especially maculopathy. Known heart failure grade III-IV of the classification of the New York Heart Association). Any type of cancer (except basal cell) in the last 5 years. Pregnancy. Refusal to give informed consent. Evidence of any other unstable or clinically significant unstable, clinically significant, immunological, endocrine, hematologic, gastrointestinal, neurological, neoplastic, or psychiatric illness. Instability or mental incompetence, so that the validity of the informed consent or the ability to complete the study is uncertain. Positive antibodies to the human immunodeficiency virus. Data on decompensated liver disease: to. Aspartate aminotransferase (AST) and / or ALT> 10 x upper limit of normal (LSN). b. Total bilirubin> 25 μmol / l (1.5 mg / dl). c. International normalized index> 1.4. d. Platelet count <100,000 / mm3. 17. Serum creatinine levels> 135 μmol / l (> 1.53 mg / dl) in men and> 110 μmol / l (> 24 mg / dl) in women. 18.Significant kidney disease, including nephrotic syndrome, chronic kidney disease (patients with markers of liver injury or estimated glomerular filtration rate [eGFR] of less than 60 ml / min / 1.73 m2). If an abnormal value is obtained at the first screening visit, the measurement of eGFR may be repeated before randomization within the following time frame: minimum 4 weeks after the initial test and maximum 2 weeks before the planned randomization. Repeated abnormal eGFR (less than 60 ml / min / 1.73 m2) leads to exclusion from the study.Pregnant or lactating women; 19. Inability to consent and/or comply with study protocol; 20. Individuals with known hypersensitivity to the study drugs. 21. Any contraindications as per the Data Sheet of or Hydroxychloroquine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled, double-blind clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testing and prophylaxis of SARS-CoV-2<br>Chemoprophylaxis with hydroxychloroquine at a dose of 200 mg twice a day for 6 months. | Drug: Hidroxicloroquina<br>* Chemoprophylaxis with hydroxychloroquine at a dose of 200 mg twice a day for 6 months.<br>|
| Active Comparator: placebo<br>Testing of SARS-CoV-2 and prescription of placebo (Hydroxychloroquine placebo) twice daily for 6 months | Drug: Control group<br>* Testing of SARS-CoV-2 and prescription of placebo (Hydroxychloroquine placebo) twice daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of new COVID-19 cases in both arms | number of new cases divided by number of persons-time at risk | From day 14 after start of treatment up to the end of follow-up: week 27 | 
| Prevalence of COVID-19 cases in both arms | percentage of cases of COVID 19 | 27 weeks after the beginning of the study | 
| Mortality rate secondary to COVID-19 cases in both groups | Case fatality rate (CFR): the proportion of diagnosed cases of COVID 19 that lead to death | 27 weeks after the beginning of the study | 
| Intensive Care Unit (CU) admission rate secondary to COVID-19 cases in both groups | percentage of patients who need admission in an ICU due to COVID 19 infection | 27 weeks after the beginning of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Presence and type of adverse events at this point. | 12 weeks after the start of treatment | 
| Adverse events | Proportion of participants that drop out of study | 27 weeks after the beginning of the study |