Intracellular boosting of human immunodeficiency virus (HIV) protease inhibitors
| ISRCTN | ISRCTN76548641 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76548641 |
| EudraCT/CTIS number | 2008-002627-90 |
| Secondary identifying numbers | 3589 |
- Submission date
- 15/09/2008
- Registration date
- 13/11/2008
- Last edited
- 21/05/2014
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
http://www.nres.nhs.uk/researchsummaries/?entryid29=177620&q=0~intracellular+boosting~
Contact information
Dr Saye Khoo
Scientific
Scientific
University of Liverpool
Pharmacology Research Labs
1st Floor, Block H
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom
Study information
| Study design | A single centre, prospective, randomised open-labelled crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Intracellular boosting of human immunodeficiency virus (HIV) protease inhibitors through inhibition of transport: a novel strategy for potentiating HIV therapy |
| Study objectives | 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(s) | Liverpool (Adult) Research Ethics Committee, 07/07/2008, ref: 08/H1005/64 |
| Health condition(s) or problem(s) studied | 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 (Persantin®; 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Lopinavir, furosemide, dipyridamole |
| Primary outcome measure | 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 study start date | 01/10/2008 |
| Completion date | 01/10/2010 |
| Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 18 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/10/2008 |
| Date of final enrolment | 01/10/2010 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Liverpool
Liverpool
L69 3GF
United Kingdom
L69 3GF
United Kingdom
Sponsor information
Royal Liverpool and Broadgreen University Hospitals Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Prescot Street
Liverpool
L7 8XP
England
United Kingdom
| Website | http://www.rlbuht.nhs.uk/ |
|---|---|
"ROR" |
https://ror.org/009sa0g06 |
Funders
Funder type
Government
National Institute of Health Research (NIHR) Biomedical Research Centre at Royal Liverpool and Broadgreen University Hospitals Trust (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
