Therapeutic Efficacy of Chloroquine Plus Primaquine in the Treatment of Uncomplicated Plasmodium Vivax

NCT06044805 | Completed Phase 4 DMC

• 1 other identifier: EPHI-IRB-294-2
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open label clinical trial will be to assess the therapeutic efficacy of chloroquine plus primaquine in the treatment of uncomplicated plasmodium vivax in Shecha Health Center, South Ethiopia. The main question it aims to answer:- the current therapeutic efficacy of chloroquine plus primaquine in the treatment of uncomplicated plasmodium vivax in Shecha Health Center, South Ethiopia based on clinical, parasitological and hematological parameter. Participants will be patients aged \>6 months with diagnosis of plasmodium vivax mono-infection and who fulfills the inclusion criteria. This is a single arm open label invivo therapeutic efficacy study of chloroquine plus primaquine in the treatment of uncomplicated plasmodium vivax. The final result will be compared with World Health Organization recommendation on antimalarial drug therapeutic efficacy.

Conditions

Efficacy; Malaria; Chloroquine; Vivax Malaria

Keywords

Therapeutic; Efficacy; Chloroquine; Primaquine; Ethiopia

Outcome Measures

Primary Outcomes (4)

• Early treatment failure [Time Frame: within the first 3 days]

  Danger signs or severe malaria on day 1, day 2 or day 3 in the presence of parasitemia;Parasitemia on day 2 higher than on day 0, irrespective of axillary temperature;Parasitemia on day 3 with axillary temperature ≥37.5 ºC;Parasitemia on day 3 ≥25% of count on day 0.

  within the first 3 days

• Late Clinical Failure (LCF)

  Danger signs or severe malaria in the presence of parasitemia on any day between day 4 and 42 in patients who did not previously meet any of the criteria of Early Treatment Failure; Presence of parasitemia on any day between 4 and day 42 with axillary temperature ≥37.5 °C (or history of fever) in patients who did not previously meet any of the criteria of Early Treatment Failure.

  42 days

• Late Parasitological Failure (LPF)

  Presence of parasitemia on any day between day 7 and day 42 and axillary temperature \<37.5 ºC in patients who did not previous meeting any of the criteria of Early Treatment Failure or Late Clinical Failure.

  42 days

• Adequate Clinical and Parasitological Response (ACPR)

  Absence of parasitemia on day 42 irrespective of axillary temperature, in patients who did not previously meet any of the criteria of Early Treatment Failure, Late Clinical Failure, or Late Parasitological Failure.

  42 days

Secondary Outcomes (5)

• The secondary outcome of this study is determining parasite clearance rate based on parasite clearance time.

  42 days

• The secondary outcome of this study is determining gametocyte clearance rate based on gametocyte clearance time.

  42 days

• The secondary outcome of this study is determining fever clearance rate based on fever clearance time.

  42 days

• The secondary outcome of this study is determining mean hemoglobin change overtime in the 42 days study period.

  42 days

• The secondary outcome of this study is evaluating the incidence of adverse events in 42 follow-up period.

  42 days

Study Arms (1)

Therapeutic Efficacy of Chloroquine Plus Primaquine

EXPERIMENTAL

An invivo single arm trial. Chloroquine (tablet containing 150mg of base) - it was given on days 0 (10mg/kg), 1(10mg/kg) and 2 (5mg/kg). Total dose, 25 mg base/kg. Primaquine - it was given once a day (0.25 mg/kg) for fourteen days, starting on day 0 of CQ treatment. Total dose, 3.5mg/kg. The medications were administered under direct observation and the patient was monitored for vomiting for 60 minutes.

Drug: Chloroquine; Drug: Primaquine

Interventions

Chloroquine DRUG

Total of 25mg base per kg over 3 days (10 mg base/kg on Days 0 and 1, 5 mg base/kg on Day 2)

Also known as: Chloroquine base, Chloroquine Phosphate

Therapeutic Efficacy of Chloroquine Plus Primaquine

Primaquine DRUG

Primaquine: 7.5 mg base tablet. Medication given as 0.25mg/kg daily for 14 days.

Therapeutic Efficacy of Chloroquine Plus Primaquine

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 6 months
• Slide confirmed infection with P. vivax with \> 250 asexual forms/μl
• Lives within 5 km of the enrolling health facility
• Weight ≥ 5.0 kg
• Ability to swallow oral medication
• Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule
• Informed consent from patient or from a parent or guardian in the case of children

You may not qualify if:

• Sever malaria with complication sign and symptoms
• Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean, symmetrical edema involving at least the feet, or mid-upper arm circumference \<100 cm for children less than five years of age
• Mixed plasmodium infection
• Severe anemia, defined as hemoglobin (Hb) \< 5 g/dl
• Presence of febrile conditions caused by diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration)
• Serious or chronic medical condition (e.g. cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS)
• Positive pregnancy test or breastfeeding
• Unable or unwilling to take contraceptives for women of child-bearing age
• Children weighing less than 5 kilograms
• History of hypersensitivity reaction to any medication tested or used as an alternative treatment
• Participants with history of prolonged QT conditions
• Taking regular medication, which may interfere with antimalarial pharmacokinetics or efficacy

Sponsors & Collaborators

• Dinka Dugassa: lead
• Ethiopian Public Health Institute: collaborator

Study Sites (1)

Shecha Health Center

Arba Minch, South Ethiopia, Ethiopia

Location

Related Publications (4)

• Fekadu G, Dugassa D, Negera GZ, Woyessa TB, Turi E, Tolossa T, Fetensa G, Assefa L, Getachew M, Shibiru T. Self-Medication Practices and Associated Factors Among Health-Care Professionals in Selected Hospitals of Western Ethiopia. Patient Prefer Adherence. 2020 Feb 20;14:353-361. doi: 10.2147/PPA.S244163. eCollection 2020.

  PMID: 32110001 BACKGROUND

• Fekadu G, Bekele F, Tolossa T, Fetensa G, Turi E, Getachew M, Abdisa E, Assefa L, Afeta M, Demisew W, Dugassa D, Diriba DC, Labata BG. Impact of COVID-19 pandemic on chronic diseases care follow-up and current perspectives in low resource settings: a narrative review. Int J Physiol Pathophysiol Pharmacol. 2021 Jun 15;13(3):86-93. eCollection 2021.

  PMID: 34336132 RESULT

• Bekele F, Fekadu G, Bekele K, Dugassa D, Sori J. Drug-related problems among patients with infectious disease admitted to medical wards of Wollega University Referral Hospital: Prospective observational study. SAGE Open Med. 2021 Jan 22;9:2050312121989625. doi: 10.1177/2050312121989625. eCollection 2021.

  PMID: 33552517 RESULT

• Fekadu G, Turi E, Kasu T, Bekele F, Chelkeba L, Tolossa T, Labata BG, Dugassa D, Fetensa G, Diriba DC. Impact of HIV status and predictors of successful treatment outcomes among tuberculosis patients: A six-year retrospective cohort study. Ann Med Surg (Lond). 2020 Nov 15;60:531-541. doi: 10.1016/j.amsu.2020.11.032. eCollection 2020 Dec.

  PMID: 33299558 RESULT

MeSH Terms

Conditions

Malaria; Malaria, Vivax

Interventions

Chloroquine; chloroquine diphosphate; Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bockretsion Gidey

  Ethiopian Public Health Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Open label clinical trial study will be conducted in Shecha Health Center from December 2022 to March 2023. Participants will be selected and treated with a 25 mg/kg standard dose of chloroquine over three days and a 0.25 mg/kg standard dose of primaquine over fourteen days. Clinical, parasitologic, and hematologic parameters will be monitored for up to a 42-day follow-up period, which will be used to evaluate therapeutic efficacy of CQ+PQ. Thick and thin blood smears will be prepared and examined to determine parasite clearance, and clinical examination will be performed over 42 follow up periods. Haemoglobin level will be measured on days 0, 14, 28 and 42. WHO double-entry Excel sheet will be used for KaplanMeier survival analysis and SPSS version-26 software will be used to analyse the data. All comparisons will be performed at 95% confidence interval and a significance level of 0.05, Pvalue of \<0.05 will be considered statistically significant

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: September 21, 2023
• Study Start: December 19, 2022
• Primary Completion: March 13, 2023
• Study Completion: March 15, 2023
• Last Updated: September 22, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ET (1)