Condition category
Infections and Infestations
Date applied
28/06/2012
Date assigned
24/07/2012
Last edited
20/05/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Dengue is a mosquito-transmitted viral infection that represents a major public health problem in Vietnam and globally. The consequences range from a symptom-free infection through to life-threatening shock and bleeding. Severe dengue infection is often caused by inflammation of the lining of blood vessels (the endothelium). There is currently no treatment for dengue beyond supportive care. Lovastatin is part of a class of drugs called statins, which were initially developed as fat (lipid)-lowering agents but have been shown to have additional benefits. Studies suggest that their use appears to be associated with an improved outcome in critically ill patients. The additional benefits include reducing inflammation of the endothelium, which could translate into a beneficial effect in dengue. Furthermore, laboratory studies have shown that lovastatin may have additional antiviral properties. These properties together with its favourable safety and cost profile make lovastatin an attractive option for dengue treatment. The main aim of the study is to formally assess the safety of using statins in patients with dengue. The study will also provide an opportunity to investigate the effect of statins on the immune response to dengue, the dengue viral load and the clinical outcome of infection.

Who can participate?
All patients aged 18 or over with a clinical suspicion of dengue, less than 72 hours of fever and a positive rapid test for dengue non-structural protein 1 (NS1) will be eligible for recruitment into the study. We have a target sample size of 330 patients.

What does the study involve?
We propose to investigate the effect of lovastatin for 5 days in adult dengue patients presenting in the first 72 hours of illness. Patients will be randomly allocated to one of two groups: one group will take lovastatin and the other group will take a dummy drug (placebo). As this is the first study investigating statin therapy in dengue with a particular focus on safety, we will use a low dose of lovastatin with the first 30 patients. If this is found to be safe we will then increase the lovastatin dose for the next 30 patients.

What are the possible benefits and risks of participating?
This is the first study exploring the use of statins in dengue. In view of this, our study has a particular emphasis on safety. Statins are very widely used and have an excellent safety profile. Rarely they can cause potentially serious problems with muscles and the liver. It is possible that these effects may occur more often in patients with dengue. We will therefore closely monitor patients to detect the development of adverse events early. In addition, patients may experience discomfort and bruising from the blood tests, although these would form part of the usual care for patients infected with dengue.
The study will pay the participants' hospital costs. If lovastatin has a beneficial effect this will potentially benefit the patients taking lovastatin as well as future patients, and will potentially benefit the community given the prevalence of dengue in Vietnam.

Where is the study run from?
The Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

When is the study starting and how long is it expected to run for?
Patients will be recruited over two dengue seasons (2012 and 2013). The study started in November 2012 and is expected to end in January 2015.

Who is funding the study?
The Wellcome Trust (UK)

Who is the main contact?
Dr James Whitehorn
jwhitehorn@oucru.org

Trial website

Contact information

Type

Scientific

Primary contact

Dr James Whitehorn

ORCID ID

Contact details

Centre for Tropical Medicine
Oxford University Clinical Research Unit
764 Vo Van Kiet Street
Ward 1
Disctrict 5
Ho Chi Minh City
00000
Viet Nam

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

26DX

Study information

Scientific title

A pilot study to investigate short-course lovastatin therapy in Vietnamese adults with dengue

Acronym

Study hypothesis

The study hypothesis is that lovastatin is safe as a short course therapy for acute dengue infections in Vietnamese subjects. This study is intended to provide preliminary information to assist in designing a possible future trial powered to assess efficacy as well as safety in the same population.

On 15/11/2012 the overall trial start date was changed from 15/07/2012 to 13/11/2012.

On 20/05/2015 the overall trial end date was changed from 15/01/2015 to 18/02/2015.

Ethics approval

1. Oxford Tropical Research Ethics Committee, 06/06/2012, OxTREC reference: 68-11
2. Hospital for Tropical Diseases Committee of Scientific and Medical Ethics, 14/03/2012, Reference Number: CS/ND/12/09

Study design

Randomized double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Dengue disease

Intervention

Current interventions as of 15/11/2012:
Patients will be assigned to one of two treatment arms:
Active Medicinal Product:
1. COHORT 1 - 40 mg lovastatin once daily for up to 5 days
2. COHORT 2 - 80 mg lovastatin once daily for up to 5 days
OR
Placebo: visually matched placebo once daily for up to 5 days

The first dose will be given as soon as practically possible after enrolment. If patients are discharged before the completion of 5 days, study drug will be stopped on this day.
The study drug will be stopped if platelets fall below 5 x 10^9/L or if the patient develops severe bleeding

Previous interventions until 15/11/2012:
Patients will be assigned to one of two treatment arms:
Active Medicinal Product:
1. COHORT 1 - 40 mg lovastatin once daily for up to 5 days
2. COHORT 2 - 80 mg lovastatin once daily for up to 5 days
OR
Placebo: visually matched placebo once daily for up to 5 days

The first dose will be given as soon as practically possible after enrolment. If patients are discharged before the completion of 5 days, study drug will be stopped on this day.

Intervention type

Drug

Phase

Not Applicable

Drug names

Lovastatin

Primary outcome measures

To evaluate the safety and tolerability of lovastatin in adult patients with dengue including rate of adverse events in each cohort

Secondary outcome measures

1. Disease progression as defined by one or more of the following:
1.1. Admission to intensive care unit
1.2. Diagnosis of shock (see definition)
1.3. Development of severe bleeding (see definition)
1.4. CNS involvement
1.5. Death
2. Fever clearance time (defined as the time from enrolment to the first time the temperature falls to < 37.5 degree C and remains below this level for 48 hours)
3. Plasma viraemia - AUC day 3 - 6 (log10-transformed)

Additional experimental endpoints include:
2. Haematological, biochemical and physiological abnormalities:
2.1. Platelet nadir between day 3 and 8 of illness
2.2. Maximum haematocrit between day 3 and 8 of illness
2.3. Percentage increase in haematocrit between day 3 and 8 of illness from baseline
2.4. Maximum alanine aminotransferase (ALT) and Creatine kinase (CK) recorded between day 3 and 8 of illness
2.5. Lowest oxygen saturation recorded between day 3 and 8 of illness
2.6. Number of patients in each group requiring colloid
3. Quality of life scores from visual analog scale during treatment (quantifiable self-measurement of quality of life in relation to personal health)
4. Virological safety parameters:
4.1. Duration from enrolment to the first undetectable viremia measurement
4.2. Duration from enrolment to first negative NS1 measurement

Overall trial start date

13/11/2012

Overall trial end date

18/02/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age > 18
2. Clinical suspicion of dengue
3. <72 hours of fever
4. Positive rapid test for dengue non-structural protein 1
5. Informed consent or assent to participate in the trial

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

330

Participant exclusion criteria

Patients with one or more of the following criteria at enrolment will be excluded from the study:
1. Signs or symptoms suggestive of any other acute infectious disease
2. Alanine aminotransferase (ALT) >150 U/L
3. Creatine kinase (CK) >1000 U/L
4. Myopathy
5. Cirrhosis
6. Use of statins within 1 week
7. Chronic use of medication contraindicated for use with lovastatin (cholestyramine, isradipine, warfarin, amiodarone, azole antifungals, fibrates, colchicine, ciclosporin, danazol, macrolides, nefazodone, niacin (high doses), protease inhibitors, verapamil, diclofenac, doxycycline, imatinib, isoniazid, nicardipine, propofol, quinidine, and diltiazem)
8. Pregnancy and lactation (all females of childbearing potential must provide urine for a âHCG test)
9. Platelet levels below 50 x 10^9/L (added as of 15/11/2012)

Recruitment start date

13/11/2012

Recruitment end date

21/01/2015

Locations

Countries of recruitment

Viet Nam

Trial participating centre

Oxford University Clinical Research Unit
Ho Chi Minh City
00000
Viet Nam

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials & Research Governance
Joint Research Office
Block 60
Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

University/education

Funder name

Wellcome Trust (UK) ref: 097430/Z/11/Z

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Funder name

Oxford University Clinical Research Unit (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2012 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/23114081

Publication citations

  1. Protocol

    Whitehorn J, Van Vinh Chau N, Truong NT, Tai LT, Van Hao N, Hien TT, Wolbers M, Merson L, Dung NT, Peeling R, Simmons C, Wills B, Farrar J, Lovastatin for adult patients with dengue: protocol for a randomised controlled trial., Trials, 2012, 13, 203, doi: 10.1186/1745-6215-13-203.

Additional files

Editorial Notes