Anti-COVID property of subcutaneous ivermectin in synergy with zinc among midlife moderately symptomatic patients: a structured summary of a study protocol for a randomised controlled trial

Trials

Yaser Masuod Alahmadi¹  Qazi Abdul Saboor²  Ayesha Humayun³  Nighat Majeed⁴  Muhammad Ghufran⁵  Rutaba Akmal⁵  Larab Kalsoom⁶  Muhammad Hassan⁷  Abeer bin Awais⁷  Mehak Gul⁷  Uzma Nasim Siddiqui⁷  Muhammad Abdul Rehman Virk⁷  Ali Ahmad⁸  Shahroze Arshad⁹  Mateen Izhar⁹  Muhammad Ahmad Imran⁹  Zaigham Habib^1,10  Iqra Farooq^1,11  Khalid Munir^1,12  Zartasha Safdar^1,13  Syed Sami Hussain Sherazi^1,13  Muhammad Ashraf^1,13  Moneeb Ashraf^1,14  Ammara Ahmad^1,15  Isra Munir^1,16  Sundas Rafique^1,17  Muhammad Kiwan Akram^1,18  Sidra Ashraf^1,19  Hamna Khalid^2,20  Sohaib Ashraf^2,21  Shoaib Ashraf^2,22 

[1] Clinical and Hospital Pharmacy Department, College of Pharmacy, Taibah University Madinah, Medina, Kingdom of Saudi Arabia;Department of Cardiology, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan;Department of Community Medicine and Public Health, Shaikh Zayed Post-Graduate Medical Complex, Lahore, Pakistan;Department of Internal Medicine, Services Institute of Medical Sciences, Lahore, Pakistan;Department of Medicine, Sahara Medical College, Narowal, Pakistan;Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan;Department of Medicine, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan;Department of Microbiology, Infectiology and Immunology, Centre Hospitalier Universitaire (CHU) Sainte Justin/University of Montreal, Montreal, Canada;Department of Microbiology, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan;Department of Orthopedics, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan;Department of Paediatric Surgery, Children Hospital, Lahore, Pakistan;Department of Pathobiology, Riphah International, Lahore, Pakistan;Department of Pharmacology and Toxicology, University of veterinary and animal sciences, Lahore, Pakistan;Department of Pharmacology, Mayo Hospital, Kingedward Medical University, Lahore, Pakistan;Department of Radiology, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan;Department of Restorative & Preventative Sciences University of Pennsylvania School of Dental Medicine University of Pennsylvania, Philadelphia, PA, USA;Department of West Medicine, Mayo Hospital, King Edward Medical University, Lahore, Pakistan;Department of animal nutrition, University of veterinary and animal sciences, Lahore, Pakistan;Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan;Specialized Sciences Post-Baccalaureate Program, College of Liberal Arts & Sciences, University of Pennsylvania, Philadelphia, PA, USA;Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA;Department of Cardiology, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan;Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA;Department of Pathobiology, Riphah International, Lahore, Pakistan;

关键词: Ivermectin;    Zinc;    Subcutaneous Ivermectin;    Pakistan;    COVID-19;    Randomised controlled trial;    protocol;   

DOI  :  10.1186/s13063-021-05487-z

来源: Springer

【 摘 要 】

ObjectivesThe study objective is to quantify the effectiveness of ivermectin (subcutaneous/oral IVM) in the presence or absence of zinc (Zn) for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients with moderate severity.Trial designThis quadruple-blinded, placebo-controlled randomized clinical trial will be a multiarmed multi-centered study with superiority framework.ParticipantsQuinquagenarian and sexagenarian patients with moderate COVID-19 symptoms and positive severe respiratory syndrome coronavirus -2 (SARS-CoV-2) PCR will be included. Participants with co-morbidities and pregnant women will be excluded.Patient recruitment will be done in Shaikh Zayed Medical Complex, Doctors Lounge and Ali Clinic in Lahore (Pakistan).Intervention and comparatorThe registered patients will be allocated in 6 groups (30 participants each). Patients will be taking subcutaneous IVM at 200 μg/kg/48 h (Arm A) or subcutaneous IVM at 200 μg/kg/48 h and oral Zn 20mg/8 h (Arm B) or oral IVM at 0.2 mg/kg/day (Arm C) or oral IVM at 0.2 mg/kg/day and oral Zn 20mg/8 h (Arm D) or alone oral Zn 20mg/8 h (Arm E) or placebo alone (Arm X). Patients in all arms will receive standard care and respective placebo (empty capsule 8 hourly and/or subcutaneous normal saline 2ml/48 h).Main outcomesPrimary endpoints will be duration of symptomatic phase and SARS-CoV-2 clearance along with high resolution CT (HRCT) chest score and clinical grade scale (CGS) on day 6. 30-day mortality will be documented as a secondary endpoint. SARS-CoV-2 clearance will be calculated by second PCR on day 7. HRCT chest score will be measured by the percentage and lung lobes involvement on day 6 with a maximum score of 25. CGS will be recorded on a seven-point scale; grade 1 (not hospitalized, no evidence of infection and resumption of normal activities), grade 2 (not hospitalized, but unable to resume normal activities), grade 3 (hospitalized, not requiring supplemental oxygen), grade 4 (hospitalized, requiring supplemental oxygen), grade 5 (hospitalized, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation), grade 6 (hospitalized, requiring ECMO and/or invasive mechanical ventilation) and grade 7 (death).RandomisationA simple lottery method will be used to randomly allocate scrutinized patients in 1:1:1:1:1:1 ratio in 6 groups.Blinding (masking)Patients, primary care physicians, outcome assessors and the data collection team will be blinded.Numbers to be randomised (sample size)180 participants will be randomized into six arms with five investigational and one placebo group.Trial StatusInstitutional Review Board Shaikh Zayed Post-Graduate Medical Complex, Lahore, Pakistan has approved the protocol (version 2.3) with ID SZMC/IRB/Internal0056/2020. The trial was approved on July 14, 2020, and enrolment started on July 30, 2020. The estimated completion date is October 30, 2021.Trial registrationClinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04472585 dated July 16, 2020.Full protocolThe 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.

【 授权许可】

CC BY