Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial
Authors: Ashraf Sohaib , Ashraf Shoaib , Akmal Rutaba , Ashraf Moneeb , Kalsoom Larab , Maqsood Aadil , Imran Muhammad Ahmad , Farooq Iqra , Ashraf Sidra , Siddiqui Uzma Nasim , Ghufran Muhammad , Akram Muhammad Kiwan , Majeed Nighat , Rafique Sundas , Habib Zaigham , Shahab Muhammad Sarmad , Akmal Adeen , Shaukat Zeeshan , Abdin Zain ul , Khaqan Ayesha , Arshad Shahroze , Rehman Virk Muhammad Abdul , Gul Mehak , Awais Abeer bin , Hassan Muhammad , Khalid Noman , Iqbal Qurrat Ul Ain , Ahmad Tausif , Akram Muaaz , Muhammad Ameer , Khalil Musa , Aslam Aneeq , Umer Muhammad , Sherazi Syed Sami Hussain , Safdar Zartasha , Ahmad Sohail , Bilal Muhammad , Zahid Muhammad Nauman , Koshak Abdulrahman E. , Hilal Abubakar , Malik Ahmad Azam , Iqbal Usman , Baig Atif Amin , Alahmadi Yaser Masuod , Humayun Ayesha , Malik Amber , Ahmad Ali , Ashraf Muhammad , Saboor Qazi Abdul , Izhar Mateen ,   DOCTORS LOUNGE consortium, Muhammad Arz , Hayat Kanwal , Amjad Ghazala , Kousar Misbah , Hafeez Umair , Mughal Tayyab , Muzafar Tayyaba , Zulfiqar Sibgha , Alam Saadia Shahzad , Anwar Muhammad Imran , Malik Amber , Mahmud Talha , Arshad Ali , Nawaz Khawar , Yousaf Muhammad Ismail Khalid 
Published: September 2021

Objectives

Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS.

Trial design

The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial.

Participants

All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study

High-risk exposure (<6 feet distance for >10min without face protection)

Moderate exposure (<6 feet distance for >10min with face protection)

Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study.

Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan).

Intervention and comparator

In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan.

Main outcomes

Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization.

Randomisation

Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure.

Blinding (masking)

Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking.

Numbers to be randomised (sample size)

1000 participants will be enrolled in the study with 1:1 allocation.

Trial Status

The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022.

Trial registration

Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087.

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.