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
Trials volume 22, Article number: 618 (2021)
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.
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.
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.
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.
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.
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.
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.
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.
Availability of data and materials
All required data will be posted along with the trial results and final trail dataset requests can be made to Dr. Sohaib Ashraf which could be available from the author on reasonable appeal subject to data protection regulations. (Twitter: SohaibAshrafMD, email address: firstname.lastname@example.org, Mobile Number: +92 3334474523)
The authors would like to acknowledge Prof. Dr. Zaheer Ahmad, PhD (Department of botany, Government College University, Lahore, Pakistan). We pay gratitude to late Prof. Dr. Zia Ullah (Internal Medicine, Shaikh Zayed Post-Graduate Medical Complex) who died while serving humanity and combating COVID-19. We are particularly grateful for the help of our local collaborators including DOCTORS LOUNGE Consortium.
DOCTORS LOUNGE Consortium
Arz Muhammad1, Kanwal Hayat1, Ghazala Amjad1, Misbah Kousar1, Umair Hafeez1, Tayyab Mughal1, Tayyaba Muzafar1, Sibgha Zulfiqar1, Saadia Shahzad Alam1, Muhammad Imran Anwar1, Amber Malik1, Talha Mahmud1, Ali Arshad2, Khawar Nawaz3, Muhammad Ismail Khalid Yousaf4
Affiliations: 1, Shaikh Zayed Post-Graduate Medical Institute, Lahore, Pakistan. 2, Kingedward Medical University, Lahore, Pakistan. 3, Sunny Downstate/Kings Country Medical Center, New York, USA. 4. University of Louisville, Kentucky, USA.
Funding by Smile Welfare Organization (SWO) - a non-profitable organization. The funder played no role in the design of the study, in the collection, analysis, and interpretation of data, and in writing the manuscript.
Ethics approval and consent to participate
The trial was approved by institutional ethical review board of Shaikh Zayed Post-Graduate Medical Complex (IRB ID # SZMC/IRB/Internal/273/2021) on February 15, 2021. Authors certify that the study has received ethical approval from the appropriate ethical committee as stated above. Before enrolment, all partakers will be fully informed of the study and asked to sign the consent form to be eligible for randomization and participation.
Consent for publication
The authors declare that they have no competing interests.
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Ashraf, S., Ashraf, S., Akmal, R. et al. 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. Trials 22, 618 (2021). https://doi.org/10.1186/s13063-021-05510-3