Protect: Study With Hydroxychloroquine for Prevention and Early Phase Treatment of Coronavirus Disease (COVID-19) (PROTECT)

PROTECT: A Randomized Study With Hydroxychloroquine Versus Observational Support for Prevention or Early Phase Treatment of Coronavirus Disease (COVID-19)

This is a Italian, superiority, open label cluster-randomised, interventional clinical trial aimed at assessing whether the treatment with Hydroxychloroquine can reduce the percentage of symptomatic subjects compared to observation only in household members/contacts of COVID-19 patients (Group 1) and if the treatment with Hydroxychloroquine could be introduced in early phase COVID-19 population (Group 2).

The participants will be randomised to receive either:

Arm A) hydroxychloroquine vs Arm B) Observation (2:1 randomisation).

Study Overview

• Status: Active, not recruiting
• Conditions: SARS-CoV-2; COVID19; Treatment; Prophylaxis; Hydroxychloroquine
• Intervention / Treatment: Drug: Hydroxychloroquine

Detailed Description

This is an open label, superiority, cluster-randomized Italian interventional clinical trial, evaluating the role of Hydroxychloroquine versus observation only in preventing infection to COVID-19 or treating early phase COVID-19 patients.

Each index case is randomised to either Arm A: Hydroxychloroquine or Arm B: observation in a 2:1 ratio on an open label basis. Participants in the same cluster receive the same intervention.

Study population is constituted by:

Group 1: Severe Acute Respiratory Syndrome (SARS) - Corona Virus (CoV)-2-exposed subjects , as household members/contacts of COVID-19 patients.

Group 2: Patients with COVID-19 asymptomatic or paucisymptomatic in home situation.

• Study Type: Interventional
• Enrollment (Anticipated): 2300
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • FC
    • Meldola, FC, Italy, 47014
      • Irst Irccs

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or Female, aged >= 18 years

2. SARS-CoV-2-exposed subjects, as household members and/or contacts of COVID-19 patients (Group 1). In this group are included Health care professionals in contact with COVID-19 patients.

   or

3. COVID-19 patients, asymptomatic or paucisymptomatic in home situation who are not in treatment with any anti COVID-19 medication (Group 2)
4. Absence of any COVID-19 symptom in last week before randomization (fever >37.5°C, cough, dyspnea) (only for group 1 subjects)
5. Paracetamol treatment is accepted only for group 2.
6. Participant is willing and able to give informed consent for participation in the study (either recorded during a telephonic interview or signed in person) and agrees with the study and its conduct.

Exclusion Criteria:

1. Reported anamnesis for:

   1. Intolerance or previous toxicity for hydroxychloroquine/chloroquine
   2. Bradycardia or reduction rhythm of heart with arrythmias
   3. Ischemic heart disease
   4. Retinopathy
   5. Congestive heart failure under/with use of diuretics
   6. Favism or glucose-6-phosphate dehydrogenase (G6PD) deficiency
   7. Diabetes type 1
   8. Major comorbidities like advanced chronic kidney disease or dialysis therapy, known history of ventricular arrhythmias, any oncologic/hematologic malignancy.
   9. Severe neurological and mental illness
2. Any other contraindication to take hydroxychloroquine
3. Already taking chloroquine, hydroxychloroquine or analogous during the past 3 weeks
4. Use of other antiviral agents in the last 3 weeks
5. Subject with a positive test for SARS-CoV-2 (for Group 1)
6. Pregnant or lactating
7. Current use of medications with known significant drug-drug interactions: digoxin, hypoglycemic agents, anticonvulsant, Cyclosporine, Phenylbutazone, drugs that inhibit CYP2D6
8. Known prolonged QT syndrome or current use of drugs with known QT prolongation
9. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Hydroxychloroquine; A loading dose Hydroxychloroquine 400 mg twice daily at day 1, followed by a weekly dose of Hydroxychloroquine 200 mg twice daily on days 8, 15 and 22, covering a total of 1 month of treatment.	Drug: Hydroxychloroquine; Hydroxychloroquine
No Intervention: Group 1: Observation; observation only
Experimental: Group 2: Hydroxycloroquine; A loading dose Hydroxychloroquine 400 mg twice daily at day 1 followed by 200 mg twice daily for a total of at least 5-7 days according to clinical evolution.	Drug: Hydroxychloroquine; Hydroxychloroquine
No Intervention: Group 2: Observation; Observation only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of subjects of Group 1 who become symptomatic and/or swab positive in each arm within 1 month from randomization.	Group 1:The primary endpoint/outcome measure is the proportion of subjects of Group 1 who become symptomatic and/or swab positive in each arm within 1 month from randomization.	within 1 month from randomization
the proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization.	Group 2: The primary endpoint/outcome measure is the proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization.	within 14 days from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with positive swabs in Group 1 within 1 month from randomization in both arms	The proportion of subjects with positive swabs in randomized population of SARS-CoV-2-exposed subjects ( Group 1) within 1 month from randomization in both arms	within 1 month from randomization
The proportion of subjects of Group 1 who become symptomatic in each arm within 1 month from randomization	The proportion of subjects of Group 1 who become symptomatic in each arm within 1 month from randomization, in subgroup population identified by stratification factors, class of age and gender.	within 1 month from randomization
The proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization.	The proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization, in subgroup population identified by stratification factors, class of age and gender.	within 14 days from randomization
The proportion of subjects of Group 2 who become swab negative in each arm within 1 month from randomization in overall population and in subgroup population	The proportion of subjects of Group 2 who become swab negative in each arm within 1 month from randomization in overall population and in subgroup population identified by stratification factors, class of age and gender.	within 1 month from randomization
Absolute and relative frequencies of Serious Adverse Events	Absolute and relative frequencies of Serious Adverse Events (CTCAE version 5.0) in both arms for the Group 1 and Group 2.	up to 10 months
Variation in Quality of Life scores in different time points	Variation in Quality of Life scores EQ-5D-5L (EQ-5D descriptive system with 5 severity levels from better to worse, and the EQ visual analogue scale (EQ VAS, scale from 100 to 0, high is better) in different time points (weekly) respect to baseline values in both Group 1 and Group 2 populations.	up to 10 months

Collaborators and Investigators

• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Collaborators: University of Bologna
• Investigators: Study Chair: Giovanni Martinelli, Prof., Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST IRCCS , Meldola Italy; Study Chair: Pierluigi Viale, Prof., Univeristy of Bologna

Publications and helpful links

General Publications

• Nanni O, Viale P, Vertogen B, Lilli C, Zingaretti C, Donati C, Masini C, Monti M, Serra P, Vespignani R, Grossi V, Biggeri A, Scarpi E, Galardi F, Bertoni L, Colamartini A, Falcini F, Altini M, Massa I, Gaggeri R, Martinelli G. PROTECT Trial: A cluster-randomized study with hydroxychloroquine versus observational support for prevention or early-phase treatment of Coronavirus disease (COVID-19): A structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Jul 31;21(1):689. doi: 10.1186/s13063-020-04527-4.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: prevention; COVID19; asymptomatic; prophylaxis; Hydroxychloroquine; Households; early phase treatment; paucisymptomatic; home situation; SARS-CoV-2-exposed subjects
• 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: IRST100.47

Drug and device information, study documents

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