Clinical efficacy of iodine complex in SARS-CoV-2-infected patients with mild to moderate symptoms: study protocol for a randomized controlled trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus-infected millions globally. Despite a wide range of advised options for the treatment of COVID-19, a single strategy to tackle this pandemic remains elusive, thus far. That is why we are conducting a clinical trial to find out the efficacy of iodine complex to clear a viral load of severe respiratory syndrome coronavirus-2 (SARS-CoV-2) along with a reduction in time taken to alleviate symptoms. METHOD: The proposed study is a placebo-controlled, add-on, randomized trial using parallel group designs. This is a closed-label and adaptive with sample size reassessment, multi-centered design with a 1:1:1:1 allocation ratio and superiority framework. It will be conducted in Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic, and Doctors Lounge, Lahore, Pakistan. This study will have three arms of mild to moderately symptomatic COVID-19 patients (50 patients in each) which will receive ionic-iodine polymer complex with 200 mg of elemental iodine: interventional arm A will have encapsulated, arm B will receive suspension syrup form, arm C will get throat spray, while arm X will be standard care with placebo. Data will be collected on self-constructed, close-ended questionnaires after obtaining written consent. Data will be analyzed using SAS version 9.4. COVID-19 patients will be monitored by RT-PCR and HRCT (high-resolution computed tomography) chest. In addition to these, the duration of the symptomatic phase and mortality benefits will be analyzed in both groups. DISCUSSION: The study is designed to measure the superior efficacy of the iodine complex as an add-on in treating COVID-19-positive patients with mild to moderate symptoms. This combination is hypothesized to improve various parameters like rapid viral load reduction, clinical and radiological improvement, lower mortality, and reduction in hospitalization. The trial will aid in devising a better strategy to cope with COVID-19 in a relatively inexpensive and accessible way. The implications are global, and this could prove itself to be the most manageable intervention against COVID-19 especially for patients from limited-resource countries with deprived socioeconomic status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04473261 . Registered on July 16, 2020.

Incessant threat of COVID-19 variants: Highlighting need for a mix of FDA-approved artificial intelligence tools and community pharmacy services.

Seamless integration of artificial intelligence (AI) technology, especially FDA-approved AI tools, in community pharmacies can build increasingly effective and easy care pathways, thereby minimizing burden on healthcare system, and ensuring compliance to preventive measure through limiting hospital visits. In this regard, the WHO needs to enlist and provide guidance on most promising AI tools that can be implemented in community pharmacy settings.

Medication adherence and persistence among patients with non-small cell lung cancer receiving tyrosine kinase inhibitors and estimation of the economic burden associated with the unused medicines.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths. Its treatment includes specific oral tyrosine kinases inhibitors (TKIs). OBJECTIVES: To estimate adherence and persistence among patients receiving TKIs and to assess the economic burden of the unused medicines in Alsace (France). METHOD: This retrospective study was carried out using the Insurance Healthcare database. MAIN OUTCOME MEASURES: Adherence was calculated using medication possession ratio (MPR), persistence using estimated level of persistence with therapy (ELPT) and economic impact using prescription refill data. RESULTS: 242 patients were receiving TKIs. The most common TKIs prescribed were erlotinib (75.6%, n = 183) and crizotinib (12.8%, n = 31). Total of 149 patients were included in the adherence analysis. Overall MPR was 0.98. 180 patients were included in the persistence analysis. Almost half of patients had stopped treatment at 60 days and only 38.3% (n = 69) were still persistent with the therapy at 120 days. The expenses related to unused TKIs amounted to €356,392 and were related majorly to treatment discontinuation followed by overlapping refills, patient deaths and dose- or drug-switching, respectively. CONCLUSIONS: Our data indicated overall adherence medicines above the acceptable limit of 0.80 but also pointed out a significant decline in persistence over time. The resulting economic losses justify the need for physicians and pharmacists to closely monitor their patients to ensure continuity of treatment. To limit the cost associated with unused medicines, interventions such as app-based monitoring, dispensing TKIs per unit over shorter periods and not only on monthly intervals could be implemented.

An in vitro antiviral activity of iodine complexes against SARS-CoV-2.

Since the emergence of COVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule)of an Iodine-complex (Renessans). First, cell cytotoxicity of Renessans on the Vero cells was determined using MTT assay. Afterwards, the antiviral activity of Renessans was determined using viral inhibition assays and TCID50. For this, nontoxic concentrations of the Renessans were used. The results showed that Renessans is nontoxic to the cells up to 50 µg/mL. At 1.5 µg/mL concentration, SARS-CoV-2 production was significantly reduced to 101.43 TCID50 and 101.58 TCID50 for the syrup and capsule, respectively, as compare to virus infected control cells 106.08 TCID50 and we found the dose dependent inhibition of virus replication in the presence of Renessans. Renessans inhibited SARS-CoV-2 with an EC50 value of 0.425 µg/mL and 0.505 µg/mL for syrup and capsule, respectively. Furthermore, there was no virus detected at concentration of 50 µg/mL of Renessans. This study indicates that Renessans, containing iodine, have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.

A quadruple blinded placebo controlled randomised trial to evaluate the effectiveness of an Iodine complex for patients with mild to moderate COVID-19 in Pakistan (I-COVID-PK): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The objective of the study is to measure the efficacy of ionic-iodine polymer complex [1] for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients. TRIAL DESIGN: The trial will be closed label, randomized and placebo-controlled with a 1:1:1:1 allocation ratio and superiority framework. PARTICIPANTS: All PCR confirmed COVID-19 adult patients including non-pregnant females, with mild to moderate disease, will be enrolled from Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Patients with any pre-existing chronic illness will be excluded from the study. INTERVENTION AND COMPARATOR: In this multi-armed study ionic-iodine polymer complex with 200 mg of elemental iodine will be given using three formulations to evaluate efficacy. Patients will be receiving either encapsulated iodine complex of 200 mg (arm A), iodine complex syrup form 40 ml (arm B), iodine complex throat spray of 2 puffs (arm C) or empty capsule (arm D) as placebo; all three times a day. All the 4 arms will be receiving standard care as per version 3.0 of the clinical management guidelines for COVID-19 established by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcomes will be viral clearance with radiological and clinical improvement. SARS-CoV-2 RT-PCR and HRCT chest scans will be done on the admission day and then after every fourth day for 12 days or till the symptoms are resolved. RT-PCR will only be shown as positive or negative while HRCT chest scoring will be done depending on the area and severity of lung involvement [2]. Time taken for the alleviation of symptoms will be calculated by the number of days the patient remained symptomatic. 30-day mortality will be considered as a secondary outcome. RANDOMISATION: Stratification for initial COVID-19 status (or days from initial symptoms as a proxy), age groups, gender, baseline severity of symptoms and co-morbidities will be used to ensure that the study arms remain balanced in size for the 1:1:1:1 allocation ratio. Randomization will be done using the lottery method. As patients are being admitted at different times, they will be recruited after obtaining their voluntary written informed consent following all standard protocols of the infection, control and disinfection. BLINDING (MASKING): This is a quadruple (participants, care providers, investigators and outcomes assessors) blinded study where only the study's Primary Investigator will have information about the arms and their interventions. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 200 patients will be randomized into four groups with three experimental and one placebo arm. TRIAL STATUS: Protocol Version Number is 2.3 and it is approved from IRB Shaikh Zayed Hospital with ID SZMC/IRB/Internal0056/2020 on July 14th, 2020. The recruitment is in progress. It was started on July 30, 2020, and the estimated end date for the trial is August 15, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04473261 dated July 16, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Adherence to oral anticancer chemotherapies and estimation of the economic burden associated with unused medicines.

Background The list of oral and expensive chemotherapy agents has lengthened over the last few years and has created unique medication adherence concerns. In a real-life setting, patients often do not take their medications as prescribed. This pattern is associated with poor outcomes and increased health care costs. Objectives To estimate the adherence to oral anticancer chemotherapies and to determine the economic burden of unused medicines due to patients' death. Setting Alsace (France). Method This retrospective study was carried out by using ERASME, an Insurance Healthcare database. Main outcome measures Adherence was calculated using medication possession ratio and economic impact using prescription refill data. Results 10,734 patients were treated with oral anticancer medicines (cytotoxic agents, hormonal and targeted therapies). Averaged adherence of 0.86 was observed although it varied significantly between subclasses (cytotoxic agents: 0.69 ± 0.14, hormonal therapy: 0.91 ± 0.17 and targeted therapy: 0.79 ± 0.17). 1631 patients died during the study period. The expenses related to unused chemotherapies amounted to €152,175. Conclusions Our data showed that overall adherence to oral anticancer medicines was above the acceptable limit of adherence of 80% with a marked graduation in values between cytotoxic agents, hormonal and targeted therapies. These statistical significant differences in medication possession ratio could be related to the intrinsic toxicity of the three subclasses of molecules, their tolerance and adverse effects. To limit the cost associated with unused medicines, interventions such as dispensing expensive oral anticancer chemotherapies per unit over shorter periods and not only on monthly intervals could be implement.