Clinical trial NCT04363827: Protect: Study With Hydroxychloroquine for Prevention and Early Phase Treatment of Coronavirus Disease (COVID-19)
Official title: PROTECT: A Randomized Study With Hydroxychloroquine Versus Observational Support for Prevention or Early Phase Treatment of Coronavirus Disease (COVID-19)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID19
Hydroxychloroquine
Prophylaxis
Treatment
SARS-CoV-2
Keywords: COVID19
Households
Hydroxychloroquine
prophylaxis
early phase treatment
prevention
asymptomatic
paucisymptomatic
home situation
SARS-CoV-2-exposed subjects
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
Collaborators: name: University of Bologna
First posted: 2020-04-27
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: the proportion of subjects of Group 1 who become symptomatic and/or swab positive in each arm within 1 month from randomization.
timeFrame: within 1 month from randomization
measure: the proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization.
timeFrame: within 14 days from randomization
Secondary outcomes:
measure: The proportion of subjects with positive swabs in Group 1 within 1 month from randomization in both arms
timeFrame: within 1 month from randomization
measure: The proportion of subjects of Group 1 who become symptomatic in each arm within 1 month from randomization
timeFrame: within 1 month from randomization
measure: The proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization.
timeFrame: within 14 days from randomization
measure: 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
timeFrame: within 1 month from randomization
measure: Absolute and relative frequencies of Serious Adverse Events
timeFrame: up to 10 months
measure: Variation in Quality of Life scores in different time points
timeFrame: up to 10 months
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: Irst Irccs
state: FC
Study officials:
affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST IRCCS , Meldola Italy
name: Giovanni Martinelli, Prof.
role: STUDY_CHAIR
affiliation: Univeristy of Bologna
name: Pierluigi Viale, Prof.
role: STUDY_CHAIR
References:
citation: 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.