Add on to Azythromycine, Phytomedicine and/or Antimalarial Drug vs Hydroxychloroquine in Uncomplicated COVID-19 Patients

Covid19 Clinical Trial

— CANCOVID-19  

Official title:

Évaluationefficacité et tolérance d'Une médication à Base de Cosphérunate et d'un phytomédicament Antiviral Par Voie Orale en Comparaison Avec un Traitement à Base d'Hydroxychloroquine Chez Des Adultes Malades Covid-19 Sans Complications

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04502342
• Other study ID #: RDIMFPG
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: June 1, 2020
• Est. completion date: September 30, 2020

Study information

• Verified date: August 2020
• Source: Institute for Research and Development of Medicinal and Food Plants of Guinea
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The phase II clinical trial, with three arms and at rate of 10 patients per arm, received the approval of the National Committee for Ethics and Health Research. This is a non inferiority test aimed to compare the efficacy and safety in add on to Azithromycin, an antimalarial drug, a treatment combination of the antimalrial drug with an antiviral phytomedicine versus Hydroxychloroquine in COVID-19 patients without complications.

During the treatment, viral clearance, adverse effects related to treatment, and symptoms progression will be assessed on days 3, 6 and 14. Clinical, paraclinical and laboratory tests will be performed throughout the 3-month trial. Ethical and deontological considerations will be applied.

Description:

The patient who has signed the informed consent for participation in the study will be immediately taken care of by the investigating clinicians. The clinician will determine the history of the disease and identify any clinical signs shown by the patient. Clinical data will be recorded in the patient's medical file. At the end of the clinical examination, the investigating clinician will draw up the report of the biological examinations.

Laboratory examinations will be carried out according to the procedures and method by accredited laboratories in Guinea (National Institute of Public Health; Hemorrhagic Fevers Laboratory; CREMS - Kindia Laboratory; Institut Pasteur de Guinée) for the diagnosis of COVID19.

After inclusion, patients are assigned by randomization into separate treatment arms with 10 patients per arm. They remain in these treatment arms for the duration of the trial, analysis, and follow-up activities. A random sequence will be generated and implemented so as to randomize.

The treatments will be made available to investigative clinicians by the Institute for Research and Development of Medicinal and Food Plants of Guinea.

All subjects meeting the inclusion criteria will benefit from an individual file which will include data relating to general information, the complete clinical examination and the paraclinical examination. The data will be coded, entered and processed using statistical software. Data entry quality control will be performed on all files. The selected patients are distributed randomly into 3 parallel arms, each arm having a different treatment modality.

A homogeneity test on the main socio-demographic variables (age, sex, weight, hemoglobin level, etc.) will be carried out between the different treatment arms before any specific analysis. Baseline characteristics and treatment of subjects in arms 1, 2 and 3 will be presented as medians, ranges for all parameters such as clinical, anthropometric, biochemical values and as percentages or numbers for symptoms. The comparison between the three cohorts will be made using either the Anova test for continuous variables or the chi2 test for categorical variables.

The rate of change over time of virologic clearance, fever and other symptom values as well as the differences for these rates between treatment arms will be tested using mixed-effects modeling.

The duration of the trial is 20 days for each patient recruited. In anticipation of future analyzes, the biological samples will be kept at the biobank of the National Institute of Public Health of Guinea.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 30
• Est. completion date: September 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• eligible patients are symptomatic adults with COVID-19 confirmed by a positive Polymerase Chain Reaction test without complications

Exclusion Criteria:

• any patient herpersensitive to hydroxychloroquine or under antimalarial treatment in the 2 weeks preceding inclusion;

• any patient with a complication who must be taken care of in an Emergency or Intensive Care Unit;

• any patient with other acute or chronic ilnesses such as heart failure, arterial hypertension, renal failure, hepatocellular failure, tuberculosis or unable to take the oral the oral treatment;

• any patient for whom one of the treatments under study is contraindicated according to the doctor's opinion;

• pregant women;

• severe neurological manifestations.

Related Conditions & MeSH terms

• Covid19

Intervention

Combination Product:
• Hydroxycloroquine and Azythromycine
dual treatment with Hydroxycloroquine and Azythromycine
• Cospherunate/Azythromycine
dual treatment with Cospherunate and Azythromycine
• Cospherunate/Phytomedicine/Azythromycien
triple treatment with Cospherunate, Asen and Azythromycine

Locations

Country	Name	City	State
Guinea	Donka; Kenien; Gbessia	Conakry

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Research and Development of Medicinal and Food Plants of Guinea

Country where clinical trial is conducted

Guinea, 

References & Publications (16)

• WHO | World Health Organization. Coronavirus (COVID-19) events as they happen [Internet]. 2020 [cited 2020 Mar 20]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen

Ayisi NK, Nyadedzor C. Comparative in vitro effects of AZT and extracts of Ocimum gratissimum, Ficus polita, Clausena anisata, Alchornea cordifolia, and Elaeophorbia drupifera against HIV-1 and HIV-2 infections. Antiviral Res. 2003 Mar;58(1):25-33. — View Citation

Baldé AM, Traoré MS, Baldé MA, Barry MS, Diallo A, Camara M, Traoré S, Kouyaté M, Traoré S, Ouo-Ouo S, Myanthé AL, Keita N, Haba NL, Goumou K, Bah F, Camara A, Diallo MS, Sylla M, Baldé ES, Diané S, Pieters L, Oularé K. Ethnomedical and ethnobotanical investigations on the response capacities of Guinean traditional health practioners in the management of outbreaks of infectious diseases: The case of the Ebola virus epidemic. J Ethnopharmacol. 2016 Apr 22;182:137-49. doi: 10.1016/j.jep.2016.02.021. Epub 2016 Feb 18. — View Citation

Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Apr;55(4):105932. doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. — View Citation

D'Alessandro S, Scaccabarozzi D, Signorini L, Perego F, Ilboudo DP, Ferrante P, Delbue S. The Use of Antimalarial Drugs against Viral Infection. Microorganisms. 2020 Jan 8;8(1). pii: E85. doi: 10.3390/microorganisms8010085. Review. — View Citation

Das AK. Anticancer Effect of AntiMalarial Artemisinin Compounds. Ann Med Health Sci Res. 2015 Mar-Apr;5(2):93-102. doi: 10.4103/2141-9248.153609. Review. — View Citation

Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJ, Marschall M. The antiviral activities of artemisinin and artesunate. Clin Infect Dis. 2008 Sep 15;47(6):804-11. doi: 10.1086/591195. Review. — View Citation

Gwitira I, Murwira A, Mberikunashe J, Masocha M. Spatial overlaps in the distribution of HIV/AIDS and malaria in Zimbabwe. BMC Infect Dis. 2018 Nov 27;18(1):598. doi: 10.1186/s12879-018-3513-y. — View Citation

Haladyj E, Sikora M, Felis-Giemza A, Olesinska M. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia. 2018;56(3):164-173. doi: 10.5114/reum.2018.76904. Epub 2018 Jun 30. Review. — View Citation

Li Y, Liu X, Guo L, Li J, Zhong D, Zhang Y, Clarke M, Jin R. Traditional Chinese herbal medicine for treating novel coronavirus (COVID-19) pneumonia: protocol for a systematic review and meta-analysis. Syst Rev. 2020 Apr 8;9(1):75. doi: 10.1186/s13643-020-01343-4. — View Citation

Liu BY, He LY, Liang ZW, Tong XY, Hu JQ, Jiao Q, Ni Q, Liu XM, Xie YM, Li P, Gao FZ, Wen TC, Liu WM. [Effect of glucocorticoid with traditional Chinese medicine in severe acute aespiratory syndrome (SARS)]. Zhongguo Zhong Yao Za Zhi. 2005 Dec;30(23):1874-7. Chinese. — View Citation

Liu DH, Liang BZ, Huang LY. [Clinical observation on the preventive effect of kangdu bufei decoction on acute severe respiratory syndrome]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Aug;24(8):685-8. Chinese. — View Citation

Mahase E. Covid-19: WHO declares pandemic because of "alarming levels" of spread, severity, and inaction. BMJ. 2020 Mar 12;368:m1036. doi: 10.1136/bmj.m1036. — View Citation

Santana Vdos S, Lavezzo LC, Mondini A, Terzian AC, Bronzoni RV, Rossit AR, Machado RL, Rahal P, Nogueira MC, Nogueira ML. Concurrent Dengue and malaria in the Amazon region. Rev Soc Bras Med Trop. 2010 Sep-Oct;43(5):508-11. — View Citation

Sohrabi C, Alsafi Z, O'Neill N, Khan M, Kerwan A, Al-Jabir A, Iosifidis C, Agha R. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). Int J Surg. 2020 Apr;76:71-76. doi: 10.1016/j.ijsu.2020.02.034. Epub 2020 Feb 26. Review. Erratum in: Int J Surg. 2020 May;77:217. — View Citation

Tong X, Li A, Zhang Z, Duan J, Chen X, Hua C, Zhao D, Xu Y, Shi X, Li P, Tian X, Lin F, Cao Y, Jin L, Chang M, Wang Y. TCM treatment of infectious atypical pneumonia--a report of 16 cases. J Tradit Chin Med. 2004 Dec;24(4):266-9. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Virological clearance of throat swabs or lower respiratory tract secretions	Virological clearance from admission to discharge at days 3, 6 and 14	day 3 to day 14
Secondary	Adverse effects	number of patients who developed treatment-related adverse effects	day 1 to day 14
Secondary	Worsened conditions	number of patients whose conditions worsened	day 1 to day 14
Secondary	COVID-19 symptoms	number of patients whose fever, cough and any other clinical sign observed on introduction have resolved	day 1 to day 14