Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000640404
Ethics application status
Approved
Date submitted
10/05/2016
Date registered
17/05/2016
Date last updated
4/06/2019
Date data sharing statement initially provided
18/03/2019
Date results information initially provided
18/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The 3-Day Malarone Schedule: Acceptability and Tolerability for Malaria Prophylaxis in Adults Travelling to Malaria Endemic Areas.
Scientific title
The 3-Day Malarone Schedule: Acceptability and Tolerability for Malaria Prophylaxis in Adults Travelling to Malaria Endemic Areas
Secondary ID [1] 289169 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 298697 0
Condition category
Condition code
Infection 298753 298753 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial will assess the use of a 3-day schedule of Atovaquone-Proguanil (250/100mg per tablet) for malaria prophylaxis. The modified schedule involves taking 4 tablets per day for 3 consecutive days to provide protection for one month. The 3-day schedule will be completed at least 2-5 days prior to leaving Australia, depending on duration of travel, itinerary, and convenience. A travel medicine nurse will contact the traveller by phone prior to departure from Australia to monitor adherence to the recommended schedule. If a traveller is unable to tolerate the 3-day schedule, alternative malaria chemoprophylaxis will be arranged prior to departure.
Intervention code [1] 294692 0
Prevention
Intervention code [2] 294729 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298234 0
Tolerability of the 3-day schedule of Atovaquone-Proguanil for malaria prophylaxis. Tolerability will be assessed using a memory aid and symptom diary (4-point Likert Scale) to record the frequency and severity of adverse events.
Timepoint [1] 298234 0
One week after travellers return from overseas travel to malaria-endemic area.
Primary outcome [2] 298270 0
Acceptability of the 3-day schedule of Atovaquone-Proguanil for malaria prophylaxis. Acceptability will be assessed during post-travel telephone interviews to be conducted by travel health nurses. Travellers will be asked if they would choose to take the 3-day Malarone schedule again if travelling to another malaria endemic area in the future, and the reasons for their decision including considerations related to convenience and cost.
Timepoint [2] 298270 0
One week after travellers return from overseas travel to malaria-endemic area.
Primary outcome [3] 298271 0
Compliance with the 3-day schedule of Atovaquone-Proguanil for malaria prophylaxis. Compliance will be assessed during pre-travel telephone interviews to be conducted by travel health nurses. Nurses will call each traveller prior to departure to ask whether the 3-day schedule of tablets had been taken properly. If not, the reasons for non-compliance will be ascertained. If travellers were unable to complete the 3-day schedule because of adverse events, alternative chemoprophylaxis will be arranged prior to travel.
Timepoint [3] 298271 0
One week after travellers return from overseas travel to malaria-endemic area.
Secondary outcome [1] 323621 0
Prevalence of adverse events from 3-day schedule of Malarone. The most common adverse events include nausea, vomiting, abdominal pain, diarrhoea, headache, and mouth ulcers. Adverse events will be assessed using a 4-point Likert Scale in a symptom diary.
Timepoint [1] 323621 0
One week after travellers return from overseas travel to malaria-endemic area.

Eligibility
Key inclusion criteria
1. Over 18 years of age
2. Travelling to a malaria-endemic area in Asia, Pacific Islands, and South/Central
America for 4 weeks or less
3. Able to give written Informed Consent and sign consent after all aspects of the
protocol explained
4. Subject must agree to participate in all planned follow-up telephone reviews, and to
return their Memory Aid and Diary to their travel clinic.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Previous adverse reactions to Malarone
2. Taking other medications that adversely interact with Malarone (metoclopramide,
rifampicin and tetracyclines may decrease the efficacy of Atovaquone; fluvoxamine may
decrease the efficacy of Proguanil).
3. Pregnancy or planning pregnancy.
4. Significant medical conditions including diabetes, heart problems, asthma, epilepsy,
depression, renal impairment, gastrointestinal disorders, and those taking long-term
antibiotics.
5. Travelling to highly endemic countries with a high risk of malaria, e.g Sub-Saharan
Africa.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2016
Actual
25/10/2016
Date of last participant enrolment
Anticipated
Actual
1/03/2018
Date of last data collection
Anticipated
31/05/2018
Actual
31/05/2018
Sample size
Target
222
Accrual to date
Final
232
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA

Funding & Sponsors
Funding source category [1] 293556 0
Self funded/Unfunded
Name [1] 293556 0
Unfunded
Country [1] 293556 0
Primary sponsor type
Individual
Name
Colleen Lau
Address
Department of Global Health
Research School of Population Health
Australian National University,
Building 62, Mills Road
Canberra, ACT 0200

Postal address:
Dr Colleen Lau
P O Box 2726,
New Farm, QLD 4005
Country
Australia
Secondary sponsor category [1] 292371 0
Individual
Name [1] 292371 0
Dr Deborah Mills
Address [1] 292371 0
Dr Deb The Travel Doctor
5th Floor, 247 Adelaide St,
Brisbane, QLD 4000
Country [1] 292371 0
Australia
Other collaborator category [1] 278995 0
Individual
Name [1] 278995 0
Ms Lani Ramsay
Address [1] 278995 0
Travel-Bug Vaccination Clinic
182 Ward St
Adelaide, SA 5006
Country [1] 278995 0
Australia
Other collaborator category [2] 278996 0
Individual
Name [2] 278996 0
Dr Andrew Ebringer
Address [2] 278996 0
Senior Medical Director
International SOS
Level 27, 288 Edward St
Brisbane, QLD 4000
Country [2] 278996 0
Australia
Other collaborator category [3] 280055 0
Other
Name [3] 280055 0
Travel Medicine Centre Perth
Address [3] 280055 0
Ground Floor, 5 Mill St,
Perth WA 6000
Country [3] 280055 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294993 0
Human Research Ethics Committee, Australian National University
Ethics committee address [1] 294993 0
Research Integrity & Compliance,
Research Services,
Ground Floor, Chancelry 10B
Ellery Crescent,
The Australian National University
ACTON ACT 2601
Ethics committee country [1] 294993 0
Australia
Date submitted for ethics approval [1] 294993 0
09/05/2016
Approval date [1] 294993 0
25/08/2016
Ethics approval number [1] 294993 0
2016087

Summary
Brief summary
Malaria is one of the most common causes of fever in Australian travellers, with approximately 400 cases reported each year in Australia. In addition, some travellers develop malaria and seek treatment while overseas, and are not included in these reported numbers. Most travellers who develop malaria did not take anti-malarial medications, or did not take the medications properly (e.g. forgot to take tablets). Malaria is a serious illness, and could potentially be life-threatening if not treated promptly. Antimalarial medications reduce the risk of malaria by about 90%, and the most commonly used options in Australia are Malarone, Doxycycline, and Mefloquine (Lariam). This research project aims to reduce the risk of malaria in travellers by improving compliance with anti-malarial medications. We propose to test the acceptability and tolerability of a 3-day schedule of a malaria medication called Malarone. Currently, travellers are required to take Malarone daily, starting 2 days before travel to a malaria risk area and continuing until 7 days after leaving the area. With the 3-day schedule, travellers will only need to take medications for 3 days and be protected for 4 weeks. The schedule will likely improve compliance and therefore reduce the risk of malaria. For trips that are of 4 weeks duration or less, travellers will be able to complete their antimalarial medications before leaving home, and not worry about carrying or taking tablets during their trip.
Trial website
Trial related presentations / publications
Public notes
The Malarone tablets will be paid for by each individual traveller (or their employer for work-related trips), just as travellers would normally pay for any malaria chemoprophylaxis. This study has not received funding for medications from the clinics, doctors, researchers, pharmaceutical companies, or any other third parties.
Attachments [1] 875 875 0 0
/AnzctrAttachments/370664-2016087_Lau_Study Protocol_3MT.pdf

Contacts
Principal investigator
Name 65714 0
Dr Colleen Lau
Address 65714 0
Department of Global Health
Research School of Population Health
Australian National University
Building 62, Mills Road
Canberra, ACT 0200
Country 65714 0
Australia
Phone 65714 0
+61 402134878
Fax 65714 0
Email 65714 0
[email protected]
Contact person for public queries
Name 65715 0
Dr Colleen Lau
Address 65715 0
Department of Global Health
Research School of Population Health
Australian National University
Building 62, Mills Road
Canberra, ACT 0200
Country 65715 0
Australia
Phone 65715 0
+61 402134878
Fax 65715 0
Email 65715 0
[email protected]
Contact person for scientific queries
Name 65716 0
Dr Colleen Lau
Address 65716 0
Department of Global Health
Research School of Population Health
Australian National University
Building 62, Mills Road
Canberra, ACT 0200
Country 65716 0
Australia
Phone 65716 0
+61 402134878
Fax 65716 0
Email 65716 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDrug-free holidays: Compliance, tolerability, and acceptability of a 3-day atovaquone/proguanil schedule for pretravel malaria chemoprophylaxis in australian travelers.2019https://dx.doi.org/10.1093/cid/ciy854
N.B. These documents automatically identified may not have been verified by the study sponsor.