Condition category
Infections and Infestations
Date applied
15/09/2008
Date assigned
13/11/2008
Last edited
21/05/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Contact information

Type

Scientific

Primary contact

Dr Saye Khoo

ORCID ID

Contact details

University of Liverpool
Pharmacology Research Labs
1st Floor
Block H
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom

Additional identifiers

EudraCT number

2008-002627-90

ClinicalTrials.gov number

Protocol/serial number

3589

Study information

Scientific title

Intracellular boosting of human immunodeficiency virus (HIV) protease inhibitors through inhibition of transport: a novel strategy for potentiating HIV therapy

Acronym

Study hypothesis

The intracellular accumulation of the HIV protease inhibitor lopinavir may be pharmacologically enhanced in-vivo through inhibition of drug transporters using dipyridamole and furosemide.

Ethics approval

Liverpool (Adult) Research Ethics Committee, 07/07/2008, ref: 08/H1005/64

Study design

A single centre, prospective, randomised open-labelled crossover study

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

Human immunodeficiency virus (HIV) pharmacology

Intervention

During the study period, patients will continue to take their normal antiretroviral therapy including lopinavir. Following screening subjects will attend at study visit 1 for a 12 hour pharmacokinetic assessment. Subjects will return the next day for study visit 2 and receive a stat dose of either furosemide 40 mg or dipyridamole modified release (PersantinĀ®; Retard) 200 mg followed by a 12 hour pharmacokinetic assessment. After a 7 day washout period, subjects will return for study visit 3 and receive a stat dose of either furosemide 40 mg or dipyridamole MR 200 mg followed by a 12 hour pharmacokinetic assessment. After a 7 day washout period subjects will return for study visit 4 and receive stat doses of both furosemide 40 mg and dipyridamole MR 200 mg followed by a 12 hour pharmacokinetic assessment. Following a 7 day washout period subjects will attend for a clinical assessment (study visit 4).

Updated 21/05/2014: this trial was stopped early on 29/02/2012 due to slow recruitment and safety concerns.

Intervention type

Drug

Phase

Not Specified

Drug names

Lopinavir, furosemide, dipyridamole

Primary outcome measures

A change in cellular accumulation ratio (CAR) of lopinavir following treatment with dipyridamole and/or furosemide. CAR will be calculated as a ratio of intracellular and plasma area under curve (AUC) of lopinavir.

The outcomes will be measured at the study visits 1, 2, 3 and 4 by pharmacokinetic assessment. Serial blood specimens will be obtained at trough, 1, 2, 4, 8, 12 hours post lopinavir dose.

Secondary outcome measures

1. Absolute change in plasma AUC
2. Absolute change in intracellular AUC
3. Safety and tolerability of furosemide and dipyridamole
4. Correlation between drug transporter expression on peripheral blood mononuclear cells (PBMCs) at baseline and
4.1. Intracellular drug exposure
4.2. Intracellular boosting effect of furosemide and/or dipyridamole
4.3. Polymorphisms in host genotype of transporter

The outcomes will be measured at the study visits 1, 2, 3 and 4 by pharmacokinetic assessment. Serial blood specimens will be obtained at trough, 1, 2, 4, 8, 12 hours post lopinavir dose.

Overall trial start date

01/10/2008

Overall trial end date

01/10/2010

Reason abandoned

Participant recruitment issue

Eligibility

Participant inclusion criteria

1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
2. Male or female patients
3. Aged 18 years and above
4. HIV positive

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

18

Participant exclusion criteria

1. History of drug sensitivity or drug allergy to lopinavir, ritonavir, furosemide or dipyridamole
2. Aged less than 18 years
3. Pregnant or lactating women
4. CD4 less than 100 x 10^6 L
5. Viral load greater than 5000 copies
6. Anaemia (haemoglobin [Hb] less than 10.0 g/dl)
7. Severe coronary artery disease
8. Unstable angina
9. Recent myocardial infarction or haemodynamic instability
10. Hypovolaemia or dehydration
11. Renal dysfunction (estimated glomerular filtration rate [eGFR] less than 70 ml/min/1.73 m^2)
12. Severe hypokalaemia (K+ less than 3.0 mmol/l)
13. Severe hyponatraemia (Na+ less than 130 mmol/l)
14. Men with symptomatic urinary outflow obstruction
15. Severe hypotension (systolic less than 100 mmHg or diastolic less than 60 mmHg)
16. Women of childbearing age unless using appropriate contraception
17. Any known bleeding disorders
18. International normalised ratio (INR) less than 1.5
19. Platelets less than 100 x 10^9 L

Recruitment start date

01/10/2008

Recruitment end date

01/10/2010

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Liverpool
Liverpool
L69 3GF
United Kingdom

Sponsor information

Organisation

Royal Liverpool and Broadgreen University Hospitals Trust (UK)

Sponsor details

Prescot Street
Liverpool
L7 8XP
United Kingdom

Sponsor type

Government

Website

http://www.rlbuht.nhs.uk/

Funders

Funder type

Government

Funder name

National Institute of Health Research (NIHR) Biomedical Research Centre at Royal Liverpool and Broadgreen University Hospitals Trust (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

Publication citations

Additional files

Editorial Notes