Effectiveness of Mass Drug Administration for Reducing Seasonal Malaria Transmission in Zanzibar

Malaria Clinical Trial

— MaDrAZ  

Official title:

Effectiveness of Mass Drug Administration (MDA) for Reducing Seasonal Malaria Transmission Towards Its Elimination in Hotspot Areas in Zanzibar - a Cluster-randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02721186
• Other study ID #: MaDrAZ-001
• Secondary ID: ZAMREC/0001/Janu
• Status: Completed
• Phase: N/A
• First received: March 17, 2016
• Last updated: October 3, 2017
• Start date: April 30, 2016
• Est. completion date: September 30, 2017

Study information

• Verified date: October 2017
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall aim of this study is to determine the effectiveness of two rounds of mass drug administration (MDA) with dihydroartemisinin-piperaquine (DHAp) + single low dose (SLD) primaquine for reducing seasonal malaria transmission in Shehias considered hotspots on Unguja Island, Zanzibar.

Description:

Study design: This is a cluster-randomised controlled study with two arms: an intervention arm with two rounds of MDA with dihydroartemisinin-piperaquine (DHAp) + single low dose (SLD) primaquine, and a control arm with no MDA.

Study site and study population: The study will be conducted in 16 hotspot Shehias (8 Shehias randomly allocated to each arm), in three districts (West, Central and South districts) in Unguja Island, Zanzibar. Hotspot Shehias [Shehia being the smallest administrative structure in Zanzibar] are defined as Shehias with an annual malaria incidence of >0.8%, calculated as the number of confirmed malaria infections notified at health facilities and during active case detection in 2015 / Shehia projected population for 2015. The study population will include all consenting residents of the selected Shehias, reaching approximately 24000 people.

Study implementation: Two rounds of MDA with DHAp (D-ARTEPP, Guilin Pharmaceutical (Shanghai) Co., Ltd., China) and SLD (0.25mg/kg) primaquine (Primaquine, Remedica Ltd.,Cyprus ) will be conducted approximately four weeks apart in the intervention Shehias, at the anticipated lowest point of malaria transmission prior to the onset of malaria transmission associated with the main rains in April-June 2016. The first drug dose including DHAp and SLD primaquine will be given under supervision whenever possible; the other two doses of the standard once daily DHAp regimen will be taken unsupervised at home. Labelled packets containing all three doses will be left with the head of household with clear instructions for individuals not present at the time of the household visit.

Study objectives: The primary objective of the study is to determine the effectiveness of two rounds of MDA with DHAp + SLD primaquine for reducing seasonal malaria transmission in Shehias considered hotspots on Unguja Island, Zanzibar. The secondary objectives of the study include determining MDA coverage, compliance, and safety after one and two rounds of DHAp + SLD primaquine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22500
• Est. completion date: September 30, 2017
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months and older

Eligibility

Inclusion Criteria:

• Permanent or temporary resident of study Shehias (i.e., persons who stayed in the selected household the night before the interview)

• Provision of informed consent (refusal must be recorded)

• Age >6 months

Exclusion Criteria:

• Women pregnant in first trimester (assessed by a specific set of questions designed to exclude pregnancy)

• Severe disease that requires immediate referral to health facility or hospital

• Concurrent antimalarial treatment at time of MDA or during the last 14 days

• Inability to take oral medication

Additional exclusion criteria for treatment with SLD Primaquine:

• Pregnancy (all trimesters, assessed by a specific set of questions designed to exclude pregnancy)

• Women breast feeding infants aged < 6months

Related Conditions & MeSH terms

• Malaria
• Plasmodium Infections

Intervention

Drug:
• MDA with DHAp and SLD Primaquine

Locations

Country	Name	City	State
Tanzania	Zanzibar Malaria Elimination Programme	Mwanakwerekwe	Urban District, Zanzibar

Sponsors (7)

Lead Sponsor	Collaborator
Ulrika Morris	Mahidol Oxford Tropical Medicine Research Unit, RTI International, The President’s Malaria Initiative, University of California, San Francisco, Uppsala University, Zanzibar Malaria Elimination Programme

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Population coverage of the MDA intervention at each round	MDA coverage determined as the number of administered DHAp and SLD primaquine doses during the first and second round of MDA, over over the Shehia population size determined by population enumeration at the time of the intervention.	Through completion of first and second round of MDA, i.e. 15 days and 48 days after initiation of MDA, respectively.
Other	Proportion of population receiving two rounds of MDA	The proportion of the population having received zero, one or two rounds of MDA. Refusal and reason for refusal to participate will be recorded.	Through completion of the second round of MDA, i.e. 48 days after initiation of MDA.
Other	Population compliance to the MDA intervention at each round	MDA compliance, i.e. the proportion of the population that have taken one, two or all three doses of DHAp + SLD primaquine, will be evaluated in a subset of the population by post-MDA surveys conducted seven days after the initiation of each MDA round. The post MDA surveys will include both a questionnaire and finger prick blood sampling for measuring piperaquine blood concentrations.	7 days after both first and second round of MDA
Other	Occurence of adverse events after MDA with DHAp and SLD primaquine	A brief questionnaire will be conducted in a subset of the population during post-MDA surveys conducted seven days after the initiation of each MDA round. The questionnaire will include specific questions regarding adverse events such as vomiting, nausea, gastrointestinal upset, rash and fatigue. Severe adverse events, especially symptoms of haemolysis, will be captured at health facilities where haemoglobin and dark urine (representing haemolysis) will be measured and reported using the pharmacovigilance forms and the Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT) developed by the Global Health Group at University of California San Francisco.	14 days after both first and second round of MDA
Other	Cumulative notified malaria incidence in the MDA and control Shehias during the following high transmission season.	Cumulative notified malaria incidence during the following high transmission season, monitored through the malaria case notification system, to assess the long-term effectivness of MDA.	15 months after second round of MDA
Primary	Cumulative notified malaria incidence in the MDA and control Shehias	Cumulative notified malaria incidence determined as the number of confirmed malaria cases notified at health facilities (monitored through the malaria case notification system during the period of six months) over the Shehia population size determined by population enumeration at the time of the intervention.	6 months after second round of MDA
Secondary	PCR determined community prevalence of Plasmodium infections in the MDA and control Shehias	PCR determined community prevalence of Plasmodium infections determined by cross-sectional screening in every other household in the study area at the time of the first round of MDA, and at six months after the second round of MDA.	Baseline and 3 months after second round of MDA