The efficacy of N-Acetylcysteine in severe COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial

Objectives: Severe acute respiratory infection (SARI) caused by the SARS-CoV-2 virus may cause lung failure and the need for mechanical ventilation. Infection with SARS-COV-2 can lead to activation of inflammatory factors, increased reactive oxygen species, and cell damage. In addition to mucolytic effects, N-Acetylcysteine has antioxidant effects that we believe can help patients recover. In this study, we evaluate the efficacy of N-Acetylcysteine in patients with severe COVID-19. Trial design: This is a prospective, randomized, single-blinded, phase 3 controlled clinical trial with two arms (ratio 1:1) parallel-group design of 40 patients, using the placebo in the control group. Participants: All severe COVID-19 patients with at least one of the following five conditions: (respiration rate > 30 per minute), hypoxemia (O2 � saturation, arterial oxygen partial pressure ratio 50 of lung area during 24 48 h), Lactate dehydrogenase (LDH) > 245 U / l, Progressive lymphopenia, and admitted to the intensive care unit of Shahid Mohammadi Hospital in Bandar Abbas and have positive PCR test results for SARS-Cov-2 and sign the written consent of the study will be included. Patients will be excluded from the study if they have a history of hypersensitivity to N-Acetylcysteine, pregnancy, or refuse to participate in the study. Intervention and comparator: After randomization, participants in the intervention group receive standard of care (SOC) according to the National Committee of COVID-19 plus N-acetylcysteine (EXI-NACE 200mg/mL, in 10mL ampules of saline for parenteral injection (EXIR pharmaceutical company)) at a dose of 300 mg/kg equivalent to 20 gr as a slow single intravenous injection on the first day of hospitalization. In the control group patients receive SOC and placebo (Sterile water for injection as the same dose). The placebo is identical in appearance to the N-acetylcysteine injection (EXIR pharmaceutical company as well). Main outcomes: The primary endpoint for this study is a composite endpoint for the length of hospitalization in the intensive care unit and the patient's clinical condition. These outcomes were measured at the baseline (before the intervention) and on the 14th day after the intervention or on the discharge day. Randomisation: Eligible participants (40) will be randomized in two arms in the ratio of 1: 1 (20 per arm) using online web-based tools and by permuted block randomization method. To ensure randomization concealment, random sequence codes are assigned to patients by the treatment team at the time of admission without knowing that each code is in the intervention or comparator group. Blinding (masking): All participants will be informed about participating in the study and the possible side effects of medication and placebo. Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. Numbers to be randomised (sample size): A total of 40 patients participate in this study, which are randomly divided; 20 patients in the intervention group will receive SOC and N-acetylcysteine, 20 patients in the control group will receive SOC and placebo. Trial status: First version of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on February 14, 2021, with the local code 990573, and the recruitment started on March 2, 2021 and the expected recruitment end date is April 1, 2021. Trial registration: The protocol was registered before starting participant recruitment entitled: Evaluation of the efficacy of N-Acetylcysteine in severe COVID-19 patients: a randomized controlled phase III clinical trial, IRCT20200509047364N3, at Iranian Registry of clinical trials on 20 February 2021. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar 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 (Additional file 2). © 2021, The Author(s)

The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial

Objectives: This study aims to investigate the effect of Famotidine on the recovery process of COVID-19 patients. Trial design: This phase III randomized clinical trial was designed with two parallel arms, placebo-controlled, single-blind, and concealed allocation. Participants: All COVID-19 patients admitted to Shahid Mohammadi Hospital in Bandar Abbas whose PCR test results are positive for SARS-Cov-2 and sign the written consent of the study are included in the study and immunocompromised patients, end-stage renal disease, moderate renal failure (clearance Creatinine 30 to 50 ml/min) or stage 4 severe chronic kidney disease or need for dialysis (creatinine clearance lesser than 30 ml/min), history of liver disease, hepatitis C infection or alcoholism, Glucose 6 phosphate dehydrogenase deficiency(G6PD), the ratio of Alanine transaminase to Aspartate transaminase 5 times above the normal limit, history or evidence of long QT segment on Electrocardiogram, psoriasis or porphyria, pregnancy, use of oral contraceptives, Dasatinib, Neratinib, Ozanimod, Pazopanib, Rilpivirine, Siponimod and/or Tizanidine and allergies to any study drug are excluded. Intervention and comparator: Intervention group receives standard pharmacotherapy according to the treatment protocols of the National Committee of COVID-19 and oral famotidine 160 mg (Manufactured by Chemidarou Pharmaceutical Company) four times a day until the day of discharge, for a maximum of fourteen days. Comparator group receives standard drug therapy according to the treatment protocols of the National Committee of COVID-19 and placebo in the same dosage. Main outcomes: Patients� temperature, respiration rate, oxygen saturation, lung infiltration, lactate dehydrogenase and complete blood count were measured at the baseline (before the intervention) and on day 14 after the intervention or on the discharge day. Randomisation: The person who has no role in admitting patients and assigning patients to random codes preparing random sequences using online tools and by permuted block randomization method. Eligibility criteria are monitored by the person responsible for admitting patients. Codes in a random sequence are assigned to patients by the treatment team without knowing that each code is in the intervention or comparator group. Patient codes are then matched to randomly generated sequence information for interventions. Blinding (masking): All participants are unaware of which group of this study they are in and after grouping patients in the groups, Patients receive Famotidine in the treatment group and receive a placebo in the control group. The lead researcher, care givers, data collectors, and outcome assessors are aware of the grouping of patients. Numbers to be randomised (sample size): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. A total of 20 patients participate in this study, which are randomly divided into two groups of 10 as intervention or control groups. Trial status: Version 3 of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on August 2, 2020, with the local code 990245, and the recruitment started on August 17, 2020. recruitment ended on August 31, 2020. Since the recruitment ended earlier than expected (the expected recruitment end date was 21/12/2020), we submitted post recruitment but prior to publication of the results. Trial registration: The protocol was registered before starting subject recruitment under the title: The effect of Famotidine on the improvement of patients with COVID-19, IRCT20200509047364N2, at Iranian Registry of clinical trials (https://www.irct.ir/trial/49657) on 17 August 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar 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 (Additional file 2). © 2020, The Author(s)

Evaluation of the efficacy and safety of recombinant erythropoietin on the improvement of hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial

Objectives: To evaluate the effect of recombinant erythropoietin on hospitalised COVID-19 patients. Trial design: Concealed, randomized, single-blinded, phase 2 controlled clinical trial with two arm parallel-group design of 20 patients allocated with 1:1 ratio and using the placebo in the control group. Participants: This study will be performed at Shahid Mohammadi Hospital in Bandar Abbas, Hormozgan in Iran. All positive (PCR confirmed) COVID-19 patients �65 years old who have Hb�9 and at least one of the severe COVID-19 symptoms (tachypnea (breathing rate> 30 beats per minute), hypoxemia (O2 �93 saturation, the partial pressure ratio of arterial oxygen <300), Lung infiltration (> 50 of lung field within 24 to 48 hours), progressive lymphopenia, LDH>245 U/I, CRP>100) and are willing to cooperate in this project will be included in the study. Patients with a history of coronary heart disease, thrombosis, deep vein thrombosis, chronic lung disease, diabetes mellitus, weakened immune system, end-stage renal disease, liver disease, and patients with a history of taking oral contraceptive pills, systolic blood pressure more than 160 mm Hg, diastolic blood pressure more than 90 mm Hg and age over 65 and erythropoietin above 500 are excluded. Intervention and comparator: Patients will receive the standard of care (SOC) based on the treatment protocols of the Iranian National Committee of COVID-19 and recombinant erythropoietin (EPREX Manufactured by Johnson and Johnson Pharmaceutical Company) 300 units / Kg or 4000IU as subcutaneous (SQ) injection three times a day for 5 days and simultaneously Enoxaparin 1 mg/kg SQ daily is also taken to prevent thrombosis in the intervention group. Patients' blood pressure, along with other vital signs, are checked regularly and at regular intervals. In the control group, patients received SOC and the placebo (distilled water) is given as a subcutaneous injection three times a day for 5 days. We use sterile water for injection (EXIRpharmaceutical company) as the placebo. To the same appearance of the placebo and the recombinant erythropoietin, they are taken in a separate room in the same size syringes and cover with labels before injection. Main outcomes: The main outcome for this study is a composite endpoint for Patient clinical symptoms (Respiratory rate, Oxygen saturation state and arterial oxygen partial pressure ratio, Lung infiltration status, blood pressure), Laboratory tests (LDH, CRP, Lymphocyte count, Endogenous erythropoietin, and Haemoglobin level). All of these will be assessed at the beginning of the study (before the intervention) and day 5 after the intervention. The study will also evaluate side effects and how to manage them. Randomisation: Eligible participants (20) will be randomized in two arms in the ratio of 1: 1 (10 per arm) by permuted block randomization method using online web-based tools. Blinding (masking): Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. Numbers to be randomised (sample size): A total of 20 patients will participate in this study, who are randomly allocated to the 2 arms with a 1:1 ratio; 10 patients in the intervention group will receive SOC and recombinant erythropoietin, and 10 patients in the control group will receive SOC and placebo. Trial Status: The protocol version is 3.0, approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on 6th June 2020, with the local grant number of 990108. The expected recruitment end date was on 21th December 2020 but since we had a wide and careful exclusion criteria because of the adverse reactions of the medication, the recruitment (for both cases and controls) was not so easy and did not finish on the expected date and we are still recruiting now. Recruitment began on 17th August 2020 and the updated expected recruitment end date is 1st August 2021. Trial registration: The protocol was registered before starting subject recruitment under the title: Evaluation of the effect of recombinant erythropoietin on the improvement of COVID-19 patients, IRCT20200509047364N1, at Iranian Registry of clinical trials (https://en.irct.ir/trial/49282) on 2020/08/09. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar 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 (Additional file 2). © 2021, The Author(s)

Durability of the two-lumen catheter in hemodialysis patients; Ethanol 70%-heparin versus cefazolin-heparin: a randomized, double-blind clinical trial study

Introduction: Maintenance of hemodialysis catheters is essential for the patients and medical staff due to their repeated use for hemodialysis and other therapeutic interventions in the hospital. Objectives: This study aimed to comprise the effect of ethanol 70%-heparin versus cefazolin-heparin on the catheter durability time of hemodialysis patients. Patients and Methods: The study population consisted of 73 hemodialysis patients referred to Shahid Mohammadi hospital in Bandar Abbas. Patients were divided into two groups cefazolin (cefazolin 5 mg/dL, and heparin 2500 IU/mL) and ethanol (ethanol 70%, and heparin 2500 IU/mL). In both groups, after each hemodialysis session, 2.9 to 3.3 mL of the locking solution was locked in the catheter lumen and remained until the next session. This intervention was conducted for all patients continuously for five months. The time of catheter durability was calculated from the time of catheter placement in the central vein until the time that it has been taken out according to the doctor’s diagnosis. Data were collected and analyzed by SPSS version 26. Results: Results showed that demographic characteristics, including age, weight, gender, marital status, catheter type, underlying diseases, and dialysis adequacy between the two groups were similar (P>0.05). In the ethanol group, the mean time of the catheter durability was 27.5 days, and in the cefazolin group was 26.98 days. Although the time of the catheter durability was slightly higher in the ethanol group, this difference was not significant (P=0.194). Conclusion: Cefazolin and ethanol 70% did not show a significant difference in the catheter durability time of hemodialysis patients. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (IRCT20210811052145N1; https://en.irct.ir/trial/58037, ethical code; IR.HUNS.REC.1398.052)

Evaluating the effect of thyroid disorders in hemodialysis patients

Background & Aims:  The thyroid gland, a small butterfly-shaped organ in the neck, regulates the body’s metabolism. Disruptions in its function can lead to various health issues, including fatigue, weight changes, and cardiovascular problems. In hemodialysis patients, thyroid function is even more crucial. Hemodialysis, a treatment for kidney failure, filters waste and excess fluid from the blood, potentially affecting various bodily systems, including the endocrine system. This study examines the effect of thyroid function on hemodialysis. Materials & Methods: In this descriptive-analytical study, dialysis patients were classified into three groups: hypothyroid, hyperthyroid, and euthyroid. The levels of thyroid and parathyroid hormones, serum electrolytes, clinical symptoms, laboratory results, and blood pressure of the patients in these groups were compared. Results: There was no significant difference between the number of dialysis sessions and thyroid function. The serum calcium level was significantly higher in hypothyroid patients than in euthyroid and hyperthyroid patients. There were no significant differences in weight changes before and after dialysis considering the participants’ sex and age (P = 0.227 and P = 0.457). Moreover, there were no significant differences in the number of dialysis sessions (P = 0.508), systolic (P = 0.419), and diastolic blood pressure (P = 0.559), or in the serum level of parathormone in patients with different thyroid functions (P = 0.103). However, the serum level of phosphorus was significantly higher in hyperthyroid patients than in normal patients and lower than in hypothyroid patients (P = 0.049). The hemoglobin concentration was higher in hyperthyroid patients than in other groups (P = 0.021). Conclusion: The changes in calcium, hemoglobin, and parathormone levels in hemodialysis patients with different thyroid function statuses showed significant differences. These differences are believed to be caused by high bone metabolism in dialysis patients. Evaluating these parameters in dialysis patients is recommended, highlighting the need for regular thyroid function screening among these patients

A Rare Variant of Turner Syndrome (the X Isochromosome-X Syndrome): A Case Report

Background: Turner syndrome occurs in nearly one in every 2000-5000 female births. This syndrome is a genetic problem in the female phenotype and the most common sex chromosome anomaly. It is diagnosed based on clinical manifestations and cytogenetic examinations. The classic syndrome (i.e., monosomy X) makes up 50% of the cases while other forms contain X chromosome variants, which do not typically manifest as the classic X phenotype. Case Presentation: This study, presents a rare variant of Turner syndrome reported in a 20-year-old woman presenting with primary amenorrhea, hypothyroidism, and short stature who had hypergonadotropic hypogonadism with hypoplastic ovaries while without the clinical manifestations of the classic Turner syndrome. The karyotype was determined as X isochromosome-X syndrome [46 XXi (Xq)]. Conclusion: This rare syndrome occurs in approximately 7% of the cases of Turner syndrome. Rare variants of the syndrome should also be considered in female patients without the classic manifestations of Turner syndrome. </jats:p