Assessment of the Efficacy of Calcium Dobesilate vs. Placebo on SARS-CoV-2 Viral Load Amongst Outpatients With COVID-19.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of CaD in reducing SARS-CoV-2 viral load in non-hospitalized adult patients diagnosed with COVID-19, documented with a positive SARS-CoV-2 PCR and with the occurrence of COVID-19 symptoms.

Detailed Description
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This study is a phase II, randomized, double-blind, placebo-controlled, monocenter trial. The study will assess the efficacy and safety of CaD compared to placebo in reducing SARS-CoV-2 viral load in non-hospitalized adult patients diagnosed with COVID-19, as well as monitoring symptoms severity, progression of the disease to severe form, and persistence of symptoms. The treatment period is seven consecutive days, followed by a 12-weeks observational period without treatment administration. Enrolled patients will be randomized, in a ratio of 1:1 into the following treatment groups: - IMP arm: patients will receive 2 x 2 capsules of Calcium Dobesilate (CaD) 500 mg (total of 2000 mg) daily for seven consecutive days - Placebo arm: patients will receive 2 x 2 capsules of matching placebo (Mannitol 500 mg) daily for seven consecutive days.

Official Title
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A Randomized, Placebo-controlled, Double-blind, Monocenter, Phase II Trial to Assess the Efficacy of Calcium Dobesilate (CaD) vs. Placebo on SARS-CoV-2 Viral Load Amongst Outpatients With COVID-19.

Conditions
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COVID-19 Virus Disease

Intervention / Treatment
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* Drug: Calcium Dobesilate
* Drug: Mannitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented COVID-19 diagnosis (SARS-CoV-2 positivity as assessed by PCR) ≤3 days of symptom appearance, with a CT<25. Symptoms related to Day 1 ≤ 5 days. Participant presents at least one of the following acute COVID-19 symptoms: nasal congestion or runny nose, sore throat, headache, myalgia, dry/productive cough, fever, chills, abdominal symptoms (nausea, vomiting, diarrhea, abdominal pain), fatigue, chest pain, palpitations, and shortness of breath. Participant is aged ≥ 16 years of age. Participant has provided an appropriate signed Informed consent. Exclusion Criteria: Known hypersensitivity or allergy to any of the study products to be administered. Participation in any other investigational device or drug study within 30 days preceding study screening visit. Treatment with Calcium Dobesilate or related molecules (e.g., ethamsylate) within 30 days preceding screening visit, or current treatment with any other investigational agent(s). Breastfeeding, unless If the patient agrees to stop breastfeeding Treatment with any investigational, emergency use authorization-approved, or approved drug for COVID-19, such as, but not limited to: monoclonal antibody treatment, direct or indirect antiviral treatment, and others according to local guidelines. Any kind of disorder or medical conditions that, in the opinion of the investigators, may be associated with increased risk to the participant, may affect patients' compliance, or may interfere with study assessments or outcomes. Inability to follow and comply with study procedures. Participant has hospitalization criteria according to local guidelines (Sat < 95%, RR >25) at the time of screening or is admitted to hospital prior to randomization Participant is, in the opinion of the investigators, likely to deteriorate in the next 24-48h and require hospitalization

Ages Eligible for Study
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Minimum Age: 16 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>The comparator (placebo, Mannitol 500 mg) will be administered orally twice a day for 7 days. | Drug: Mannitol<br>* The comparator (placebo, Mannitol 500 mg) will be administered orally twice a day for 7 days.<br>|
| Experimental: Calcium Dobesilate<br>The CaD (Calcium Dobesilate 500 mg) will be administered orally twice a day for 7 days. | Drug: Calcium Dobesilate<br>* The treatment (CaD, Calcium Dobesilate 500 mg) will be administered orally twice a day for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome | Reduction from baseline of RT-PCR SARS-CoV-2 viral load at day 4, defined by Polymerase Chain Reaction (PCR) threshold cycles. PCR reaction happens in cycles of amplification. Inclusion criteria to enter in the study is a RT-PCR positive for SARS-CoV-2, which correspond to 25 cycles (or lower) of the RT-PCR test. The participant will be tested at day 4 after treatment to evaluate if the viral load has decreased. To do that, another RT-PCR SARS-CoV-2 will be performed. A higher value of RT-PCR cycles compared to the one obtained when the participat was diagnosed COVID-19 positive, is considered a reduction from baseline. | baseline and day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 Viral Load at day 8 | Reduction from baseline of RT-PCR SARS-CoV-2 viral load at day 8. | baseline and day 8 | 
| SARS-CoV-2 Viral Load negativity | Proportion of patients with viral load negativity or very low viral load (defined by PCR threshold cycles >32) at days 4, 8 and 21. | day 4, 8 and 21 | 
| Symptoms | Time to acute symptom resolution after randomisation to treatment. Proportion of participants with acute symptom resolution at days 4, 8, 21. | day 4, 8 and 21 | 
| Symptoms resolution | Proportion of participants with acute symptom resolution at days 4, 8, 21. | day 4, 8 and 21 | 
| Persistent COVID-19 symptoms | Proportion of patients with persistent symptoms (≥1 of the following symptoms: fatigue, headache, intermittent fever, palpitations/tachycardia, sleep disturbance, anxiety, blurred vision, depression, brain fog (difficulty concentrating), loss of memory, dizziness, tinnitus (and other hearing issues), altered smell, altered taste, shortness of breath, chest pain, cough, myalgia (and spasms), neuralgias, arthralgia (joint pain), paraesthesia, nausea, vomiting, diarrhea, constipation, abdominal pain, menstrual and period problems as well as new onset of allergies) at day 84 (week 12). | day 84 | 
| Mental and physical score | SF12 score at day 21 and day 84 (week 12) compared to day 1 (baseline). | baseline and 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcium Dobesilate, Viral load, COVID-19 symptoms