Assessment of COVID‐19 Treatment containing both Hydroxychloroquine and Azithromycin: A natural clinical trial
Hassan M Abbas, Ali Azeez Al‐jumaili, Kawthar F Nassir, Muhammed Waheeb Al‐obaidy, Adnan Mohammed Al Jubouri, Basim Dhawi Dakhil, Mohammed Mahir Abdulelah, Qutaiba Ahmed Al Khames
International Journal of Clinical Practice, doi:10.1111/ijcp.13856
The goal of this study was to assess the clinical effectiveness and safety profile of the COVID-19 treatment protocol (containing both hydroxychloroquine (HCQ) and azithromycin) in an Iraqi specialised hospital.
Methods : This prospective study used a pre-and post-intervention design without a comparison group. The intervention was routine Ministry of Health (MOH) approved the management of COVID-19 for all patients. The study was conducted in a public healthcare setting in Baghdad, Iraq from March 1st to May 25, 2020. The study outcome measures included the changes in clinical and biochemical parameters during the hospitalisation period. Paired t-test and Chi-square test were used to compare the measures of vital signs, lab tests and symptoms before and after treatment.
Results: The study included 161 patients who were admitted with positive RT-PCR and clinical symptoms of COVID-19. In terms of severity, 53 (32.9%) patients had amild condition, 47 (29.2%) had moderate condition, 35 (21.7%) had severe condition and 26 (16.1%) had critical condition. Most patients (84.5%) recovered and were discharged without symptoms after testing negative with RT-PCR, while 11 (6.8%) patients died during the study period. The signs and symptoms of COVID-19 were reduced significantly in response to a therapy regimen containing HCQ and azithromycin. The most common reported side effects were stomach pain, hypoglycemia, dizziness, itching, skin rash, QT prolongation, arrhythmia, and conjunctivitis. Conclusions: This natural trial showed that the COVID-19 regimen containing both HCQ and azithromycin can be helpful to promote the recovery of most patients and reduced their signs and symptoms significantly. It also shows some manageable side effects mostly those related to heart rhythm. In the absence of FDA-approved medications to treat COVID-19, the repurposing of HCQ and azithromycin to control the disease signs and symptoms can be useful.
| INTRODUC TI ON Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus that was first recognised in Wuhan, China, in December 2019. 1 Genetic sequencing of the virus suggests that it is a beta-corona virus closely linked to the SARS virus. 2 While most people with COVID-19 develop the only mild or uncomplicated illness, approximately 14% develop a severe disease that requires hospitalisation and oxygen support, and 5% require admission to an intensive care unit. 3 In severe cases, COVID-19 can be
and symptoms is potentially useful. The study showed that using this therapy combination (HCQ and azithromycin) is promising and can fill the gap until more effective treatments are found. Future randomised controlled trial can give more definite answers about the effectiveness and safety of such therapy protocol.
ACK N OWLED G EM ENTS The authors would like to thank Dr Jawad Rasheed, Dr Ali AL-Garrawy and all the physicians and healthcare provider in Al-Shifaa Centre for Corona pandemic at Medical City, Baghdad who helped the research team conduct the study. If they had not bravely risked their lives to treat the COVID-19 cases, there would not be such a high recovery rate amongst patients.
CO N FLI C T O F I NTE R E S T No conflict of interest to declare and the study received no fund.
References
Allawi, Abbas, Rasheed, The first 40-days experience and clinical outcomes in the management of coronavirus covid-19 crisis. Single center preliminary study, J Fac Med Baghdad
Center, WHO Causality assessment, Good Pharmacovigil Pract Guid
D'acquarica, Agranat, Chiral switches of chloroquine and hydroxychloroquine: potential drugs to treat COVID-19, Drug Discov Today,
doi:10.1016/j.drudis.2020.04.021Damle, Vourvahis, Wang, Leaney, Corrigan, Clinical pharmacology perspectives on the antiviral activity of azithromycin and use in COVID-19, Clin Pharmacol Ther,
doi:10.1002/cpt.1857Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105949Guo, Cao, Hong, The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak-A n update on the status, Mil Med Res,
doi:10.1186/s40779-020-00240-0Gérard, Romani, Fresse, Off-label" use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: A survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers, Therapies,
doi:10.1016/j.therap.2020.05.002Haładyj, Sikora, Felis-Giemza, Olesinska, Antimalarialsare they effective and safe in rheumatic diseases?, Reumatologia,
doi:10.5114/reum.2018.76904Ikeda, Rokutanda, The side effect and the retention rate of hydroxychloroquine in Japan. St Luke's, Int Hosp Tokyo
Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105924Maa, Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases, Pharmacol Res Perspect,
doi:10.1002/prp2.293Mackenzie, Smith, COVID-19: A novel zoonotic disease caused by a coronavirus from China: What we know and what we don't, Microbiol Aust,
doi:10.1071/MA20013Mehra, Desai, Ruschitzka, Patel, Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, Lancet,
doi:10.1016/S0140-6736(20)31180-6Meyerowitz, Vannier, Friesen, Rethinking the role of hydroxychloroquine in the treatment of COVID-19, FASEB J,
doi:10.1096/fj.202000919O'laughlin, Mehta, Wong, Life threatening severe QTc prolongation in patient with systemic lupus erythematosus due to hydroxychloroquine, Case Reports Cardiol,
doi:10.1155/2016/4626279Ramireddy, Chugh, Reinier, Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring, medRxiv,
doi:10.1016/j.solener.2019.02.027Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A Review, JAMA-J Am Med Assoc,
doi:10.1001/jama.2020.6019Ss, COVID-19 Dashboard
Tamblyn, Clinical management of patients with moderate to severe COVID-19 -Interim Guidance
Tétu, Hamelin, Lebrun-Vignes, Prevalence of hydroxychloroquine-induced side-effects in dermatology patients: A retrospective survey of 102 patients, Ann Dermatol Venereol,
doi:10.1016/j.annder.2018.03.168Zhou, Yu, Du, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3DOI record:
{
"DOI": "10.1111/ijcp.13856",
"ISSN": [
"1368-5031",
"1742-1241"
],
"URL": "http://dx.doi.org/10.1111/ijcp.13856",
"alternative-id": [
"10.1111/ijcp.13856"
],
"assertion": [
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Received",
"name": "received",
"order": 0,
"value": "2020-06-25"
},
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Accepted",
"name": "accepted",
"order": 1,
"value": "2020-11-18"
},
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Published",
"name": "published",
"order": 2,
"value": "2020-12-05"
}
],
"author": [
{
"affiliation": [
{
"name": "Headquarter Ministry of Health Baghdad Iraq"
}
],
"family": "Abbas",
"given": "Hassan M.",
"sequence": "first"
},
{
"ORCID": "http://orcid.org/0000-0003-4691-0280",
"affiliation": [
{
"name": "College of Pharmacy University of Iowa Iowa City IA USA"
},
{
"name": "Clinical Pharmacy Department University of Baghdad College of Pharmacy Baghdad Iraq"
}
],
"authenticated-orcid": false,
"family": "Al‐Jumaili",
"given": "Ali Azeez",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-4266-3115",
"affiliation": [
{
"name": "Therapeutic Drug Monitoring Center Baghdad Teaching HospitalMedical City Complex Baghdad Iraq"
}
],
"authenticated-orcid": false,
"family": "Nassir",
"given": "Kawthar F.",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "University of Baghdad College of Medicine Baghdad Iraq"
}
],
"family": "Al‐Obaidy",
"given": "Muhammed Waheeb",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "University of Baghdad College of Medicine Baghdad Iraq"
},
{
"name": "Baghdad Teaching HospitalMedical City Teaching Complex Baghdad Iraq"
}
],
"family": "Al Jubouri",
"given": "Adnan Mohammed",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Critical Care Unit Bagdad Teaching Hospital Medical City Complex Internal Medicine Department in Al‐Shifa center for the treatment of COVID‐19 Baghdad Iraq"
}
],
"family": "Dakhil",
"given": "Basim Dhawi",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Intensive Care Unit Bagdad Teaching HospitalMedical City Complex Baghdad Iraq"
}
],
"family": "Abdulelah",
"given": "Mohammed Mahir",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Faculty of Pharmacy Philadelphia University Amman Jordan"
}
],
"family": "Al Khames",
"given": "Qutaiba Ahmed",
"sequence": "additional"
}
],
"container-title": "International Journal of Clinical Practice",
"container-title-short": "Int J Clin Pract",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"onlinelibrary.wiley.com"
]
},
"created": {
"date-parts": [
[
2020,
11,
25
]
],
"date-time": "2020-11-25T05:16:27Z",
"timestamp": 1606281387000
},
"deposited": {
"date-parts": [
[
2022,
1,
28
]
],
"date-time": "2022-01-28T06:07:03Z",
"timestamp": 1643350023000
},
"indexed": {
"date-parts": [
[
2024,
2,
23
]
],
"date-time": "2024-02-23T12:33:06Z",
"timestamp": 1708691586404
},
"is-referenced-by-count": 14,
"issue": "4",
"issued": {
"date-parts": [
[
2020,
12,
5
]
]
},
"journal-issue": {
"issue": "4",
"published-print": {
"date-parts": [
[
2021,
4
]
]
}
},
"language": "en",
"license": [
{
"URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
12,
5
]
],
"date-time": "2020-12-05T00:00:00Z",
"timestamp": 1607126400000
}
},
{
"URL": "http://doi.wiley.com/10.1002/tdm_license_1.1",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
12,
5
]
],
"date-time": "2020-12-05T00:00:00Z",
"timestamp": 1607126400000
}
}
],
"link": [
{
"URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1111/ijcp.13856",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ijcp.13856",
"content-type": "application/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1111/ijcp.13856",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "98",
"original-title": [],
"prefix": "10.1155",
"published": {
"date-parts": [
[
2020,
12,
5
]
]
},
"published-online": {
"date-parts": [
[
2020,
12,
5
]
]
},
"published-print": {
"date-parts": [
[
2021,
4
]
]
},
"publisher": "Hindawi Limited",
"reference": [
{
"DOI": "10.1186/s40779-020-00240-0",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_2_1"
},
{
"DOI": "10.1071/MA20013",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_3_1"
},
{
"article-title": "Clinical management of patients with moderate to severe COVID‐19 ‐ Interim Guidance",
"author": "Tamblyn S",
"first-page": "1",
"journal-title": "Public Heal Agency Canada",
"key": "e_1_2_10_4_1",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)30566-3",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_5_1"
},
{
"article-title": "WHO declares COVID‐19 a pandemic",
"author": "Cucinotta D",
"first-page": "157",
"issue": "1",
"journal-title": "Acta Biomed",
"key": "e_1_2_10_6_1",
"volume": "91",
"year": "2020"
},
{
"key": "e_1_2_10_7_1",
"unstructured": "And C for SS Engineering (CSSE) JHU (JHU). COVID‐19 Dashboard.https://coronavirus.jhu.edu/map.html. Published 2020. Accessed June 24 2020."
},
{
"DOI": "10.20944/preprints202004.0372.v1",
"doi-asserted-by": "crossref",
"key": "e_1_2_10_8_1",
"unstructured": "UllahMA ArafY SarkarB MoinAT ReshadRAI.Pathogenesis Diagnosis and Possible Therapeutic Options for COVID‐19.2020;https://doi.org/10.20944/PREPRINTS202004.0372.V1"
},
{
"key": "e_1_2_10_9_1",
"unstructured": "FDA.Coronavirus Treatment Acceleration Program (CTAP).https://www.FDA.gov/drugs/coronavirus‐covid‐19‐drugs/coronavirus‐treatment‐acceleration‐program‐ctap.2020. Accessed June 3 2020."
},
{
"DOI": "10.1016/j.drudis.2020.04.021",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_10_1"
},
{
"DOI": "10.3399/bjgpopen20X101069",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_11_1"
},
{
"article-title": "Clinical pharmacology perspectives on the antiviral activity of azithromycin and use in COVID‐19",
"author": "Damle B",
"first-page": "1",
"journal-title": "Clin Pharmacol Ther",
"key": "e_1_2_10_12_1",
"year": "2020"
},
{
"article-title": "The first 40‐days experience and clinical outcomes in the management of coronavirus covid‐19 crisis. Single center preliminary study",
"author": "Allawi JS",
"issue": "3",
"journal-title": "J Fac Med Baghdad",
"key": "e_1_2_10_13_1",
"volume": "61",
"year": "2019"
},
{
"article-title": "WHO Causality assessment",
"author": "Center WHO‐TUM",
"first-page": "39",
"issue": "3",
"journal-title": "Good Pharmacovigil Pract Guid",
"key": "e_1_2_10_14_1",
"year": "2009"
},
{
"DOI": "10.1016/j.ijantimicag.2020.105924",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_15_1"
},
{
"DOI": "10.5114/reum.2018.76904",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_16_1"
},
{
"DOI": "10.1016/j.puhip.2020.100004",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_17_1"
},
{
"DOI": "10.1016/j.ijantimicag.2020.105949",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_18_1"
},
{
"DOI": "10.1002/prp2.293",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_19_1"
},
{
"article-title": "Pharmacologic treatments for coronavirus disease 2019 (COVID‐19): A Review",
"author": "Sanders JM",
"issue": "18",
"journal-title": "JAMA‐J Am Med Assoc",
"key": "e_1_2_10_20_1",
"volume": "323",
"year": "2020"
},
{
"DOI": "10.1096/fj.202000919",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_21_1"
},
{
"article-title": "The side effect and the retention rate of hydroxychloroquine in Japan",
"author": "Ikeda Y",
"first-page": "A1",
"issue": "1",
"journal-title": "St Luke’s Int Hosp Tokyo, Japan",
"key": "e_1_2_10_22_1",
"volume": "5",
"year": "2018"
},
{
"DOI": "10.1016/j.annder.2018.03.168",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_23_1"
},
{
"DOI": "10.1155/2016/4626279",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_24_1"
},
{
"DOI": "10.1016/j.therap.2020.05.002",
"doi-asserted-by": "publisher",
"key": "e_1_2_10_25_1"
},
{
"article-title": "Experience with Hydroxychloroquine and Azithromycin in the COVID‐19 Pandemic: Implications for QT Interval Monitoring",
"author": "Ramireddy A",
"first-page": "1",
"issue": "1",
"journal-title": "medRxiv",
"key": "e_1_2_10_26_1",
"volume": "21",
"year": "2020"
},
{
"key": "e_1_2_10_27_1",
"unstructured": "COVID‐19 Prevention and Control 2020 Chinese Centre for Disease Control and Prevention"
},
{
"article-title": "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID‐19: a multinational registry analysis",
"author": "Mehra MR",
"journal-title": "Lancet",
"key": "e_1_2_10_28_1",
"year": "2020"
},
{
"key": "e_1_2_10_29_1",
"unstructured": "Coronavirus ( COVID‐19 ) Update : FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine Inquiries.2020;1‐3."
}
],
"reference-count": 28,
"references-count": 28,
"relation": {},
"resource": {
"primary": {
"URL": "https://onlinelibrary.wiley.com/doi/10.1111/ijcp.13856"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Assessment of COVID‐19 Treatment containing both Hydroxychloroquine and Azithromycin: A natural clinical trial",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1002/crossmark_policy",
"volume": "75"
}
