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

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID 19; Immunomediated Inflammatory Disease in Treatment With Biological Agents and / or Jak Inhibitors
• Intervention / Treatment: Drug: Hidroxicloroquina; Drug: Control group

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who meet the requirements of the New Coronavirus Infection Diagnosis (Acute respiratory infection symptoms or acute cough alone and positive PCR)
2. Aged ≥18 and < 75 years male or female;
3. In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
4. Willing to take study medication
5. Willing to comply with all study procedures,
6. Diagnosis of IBD disease, rheumatoid arthritis, seronegative spondyloarthritis or psoriasis for more than 6 months.
7. 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
8. Able to provide oral and written informed consent

Exclusion Criteria

1. Previous infection with SARS-CoV-2.
2. Current treatment with hydroxychloroquine / chloroquine.
3. Previous or current treatment with tamoxifen or raloxifene.
4. Previous eye disease, especially maculopathy.
5. Known heart failure grade III-IV of the classification of the New York Heart Association).
6. Any type of cancer (except basal cell) in the last 5 years.
7. Pregnancy.
8. Refusal to give informed consent.
9. Evidence of any other unstable or clinically significant unstable, clinically significant, immunological, endocrine, hematologic, gastrointestinal, neurological, neoplastic, or psychiatric illness.
10. Instability or mental incompetence, so that the validity of the informed consent or the ability to complete the study is uncertain.
11. Positive antibodies to the human immunodeficiency virus.
12. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto de Investigación Marqués de Valdecilla

Study record dates

Study Major Dates

• Study Start (Anticipated): April 6, 2020
• Primary Completion (Anticipated): November 6, 2020
• Study Completion (Actual): August 27, 2021

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: EnCOVID-HidroxiCLOROQUINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No