Clinical Trial Evaluating Safety and Efficacy of Hydroxychloroquine and Nitazoxanide Combination as Adjuvant Therapy in Covid-19 Newly Diagnosed Egyptian Patients: A Tanta University Hope
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Tanta University
- Enrollment
- 100
- Primary Endpoint
- Number of patients with COVID-19-negative PCR
Study Overview
Brief Summary
In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China. An initial cluster of infections was linked to Huanan seafood market, potentially due to animal contact. Subsequently, human-to-human transmission occurred and the disease, now termed coronavirus disease 19 (COVID-19) rapidly spread within China and all over the world. A novel coronavirus, SARS-coronavirus 2 (SARS-CoV-2), which is closely related to SARS-CoV, was detected in patients and is believed to be the etiologic agent of the new lung disease. The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded positive sense RNA virus that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV).
Detailed Description
Selected Drugs
Hydroxychloroquine (an analog of chloroquine) has been demonstrated to have an anti-SARS-CoV activity in vitro. Hydroxychloroquine clinical safety profile is better than that of chloroquine (during long-term use) and allows higher daily dose and has fewer concerns about drug-drug interactions. Hydroxychloroquine has long-term safety (600 mg/day for 12 to 18 months was safe). Hydroxychloroquine effectively inhibited both the entry, transport and the post-entry stages of SARS-CoV-2, similar to the chloroquine, and one study found Hydroxychloroquine to be a more potent agent than chloroquine in inhibiting SARS-CoV-2 in vitro. Hydroxychloroquine acts as a weak base that can change the pH of acidic intracellular organelles including endosomes/lysosomes, essential for the membrane fusion. Besides, the significant decrease in the production of pro-inflammatory markers and cytokines with Hydroxychloroquine has made this agent a successful disease modifying anti-inflammatory agent in the treatment of various autoimmune diseases. An additional issue to be considered in severely sick patients is cytokine storm associated with disease severity of SARS-CoV-2.
There are no currently available data from randomized clinical trials (RCTs) to inform clinical guidance on the use, dosing, or duration of Hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection. Although optimal dosing and duration of Hydroxychloroquine for treatment of COVID-19 are unknown, some U.S. clinicians have reported anecdotally different Hydroxychloroquine dosing such as 400 mg twice daily on day one, then daily for 5 days; 400 mg twice daily on day one, then 200 mg twice daily for 4 days; 600 mg twice daily on day one, then 400 mg daily on days 2-5. In a recent clinical trial, Hydroxychloroquine sulfate 200 mg, three times per day during ten days was used in patients with COVID-19.
Nitazoxanide is originally developed as an antiprotozoal agent and has a broad-spectrum antiviral activity undergoing development for the treatment of influenza and other viral respiratory infections. In addition to its antiviral activity, Nitazoxanide inhibits the production of pro-inflammatory cytokines TNF-α, IL-2, IL-4, IL-5, IL-6, IL-8 and IL-10 in peripheral blood mononuclear cells. Nitazoxanide could improve outcomes in patients infected with MERS-CoV by suppressing overproduction of pro-inflammatory cytokines, including IL-6. Nitazoxanide has been tested in clinical setting for the treatment of acute uncomplicated influenza, where the subjects received either 600 or 300 mg of Nitazoxanide or placebo orally twice daily for five days and were followed for 28 days. Subjects who received Nitazoxanide 600 mg twice daily experienced shorter times to alleviation of symptoms compared with subjects who received 300 mg Nitazoxanide twice daily, which in turn, was shorter than placebo.
According to the National Health Commission of the People's Republic of China, there is lack of effective antiviral therapy against COVID-19. Nearly all patients who suffered from COVID-19-associated pneumonia accepted oxygen therapy and WHO recommended extracorporeal membrane oxygenation (ECMO) to patients with refractory hypoxemia. Rescue treatment with convalescent plasma and immunoglobulin G are delivered to some critical cases according to their condition.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Masking Description
a double blind randomized controlled parallel study
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Confirmed cases of COVID-19 (Positive RT-PCR)
- •Newly diagnosed symptomatic patients.
- •Adults (18-65 Years old)
- •Both sexes
Exclusion Criteria
- •Patients with abnormal liver function (ALT, AST), chronic kidney disease or dialysis (CrCl< 30 ml/min)
- •Pregnant women or women who are breastfeeding
- •Immunocompromised patients taking medication upon screening
- •Subjects with comorbid condition like hypertension, cardiovascular disease, diabetes mellites, asthma, COPD, malignancy
- •Patients having allergy to Hydroxychloroquine and/or Nitazoxanide
- •Patients with contraindication towards the study medication including retinopathy, G6PD deficiency and QT prolongation.
Outcomes
Primary Outcomes
Number of patients with COVID-19-negative PCR
Time Frame: within 10 days to become PCR negative
PCR analysis of COVID-19 RNA in patients
Secondary Outcomes
- Number of patients with improved respiratory rate(within 30 days)
- Number of patients with improved PaO2(within 30 days)
- Number of patients with normalized Serum IL6(within 30 days)
- Number of patients with normalized Serum TNFα(within 30 days)
- Number of patients with normalized Serum iron(within 30 days)
- Number of patients with normalized Serum ferritin(within 30 days)
- Number of patients with normalized International normalized ratio "INR" for prothrombin time(within 30 days)
- Number of patients with normalized complete blood count "CBC"(within 30 days)
- The Mortality rate among treated patients(within 30 days)
Investigators
Prof. Dr. Kamal Mohammed Okasha
Vice-President of Postgraduate Studies and Research Affairs
Tanta University