|- candidate number||6289|
|- NTR Number||NTR1940|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||10-aug-2009|
|- Secondary IDs||P09-01 METC Medisch Spectrum Enschede|
|- Public Title||Non Steroidal Anti-Inflammatory Drugs and the antiplatelet effects of acetylsalicylic acid.|
|- Scientific Title||Non Steroidal Anti-Inflammatory Drugs and the antiplatelet effects of acetylsalicylic acid.|
|- ACRONYM||NSAID's and ASA research|
|- hypothesis||While prophylactic use of acetylsalicylic acid and Non Steroidal Anti-Inflammatory Drugs (NSAIDís) is often used concomitantly for long periods of time, there is concern about the safety of this combination in preventing cardiovascular disease. There is still a debate about the inhibitory effect of NSAIDís on the cardio protective effect of acetylsalicylic acid. |
There is conflict in results of observational research, where combination of ibuprofen and acetylsalicylic acid increased, or decreased the cardiovascular risk compared to acetylsalicylic acid alone, and a pharmacodynamic study where ibuprofen inhibited the effect of acetylsalicylic acid, taken 12 hours before the acetylsalicylic dose. Based on this study, pharmacists advise to give diclofenac instead of ibuprofen in combination with acetylsalicylic acid. However, in meta-analysis on the overall risk of cardiovascular disease, diclofenac seems to be relatively harmful while naproxen tends to be relatively save. Pharmacodynamic research to the interaction between naproxen and acetylsalicylic acid, shows only a just significant inhibitory effect of naproxen on the platelet-aggregation-inhibitory effect of acetylsalicylic acid, while naproxen itself gave a strong blood-platelet-aggregation-inhibitory effect.
This is a decisive study on the potential naproxen + acetylsalicylic acid interaction.
|- Healt Condition(s) or Problem(s) studied||NSAID, Acetylsalicylzuur, Antitrombotics|
|- Inclusion criteria||Healthy volunteers.|
|- Exclusion criteria||1. Use of medicins of any kind (also alternative medicins) except for oral contraceptives;|
2. Allergy to acetylsalicylic acid and / or NSAIDís;
3. History of stomach ulcer(s) or stomach bleeding;
4. History of stroke;
5. Cardiovascular disease;
6. Renal insufficiency;
10. Von Willebrandís disease;
11. Pregnancy, or or current pregnancy wish.
|- mec approval received||no|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||9-jan-2009|
|- planned closingdate||9-jan-2010|
|- Target number of participants||30|
|- Interventions||Subjects will receive 2 doses of etoricoxib 90 mg and meloxicam 15 mg, or 3 doses of naproxen 500 mg and ibuprofen 600 mg, mg (one NSAID per cycle). Subjects will also receive three times one dose of acetylsalicylic acid 80 mg (one during each cycle). As a comparator subjects will receive 3 times one placebo tablet (during one of the three cycles). |
|- Primary outcome||To measure the pharmacodynamic interaction between naproxen + acetylsalicylic acid as compared to the placebo + acetylsalicylic interaction. Also the pharmacodynamic interaction between acetylsalicylic acid and other in The Netherlands often used NSAID's will be examined: ibuprofen, meloxicam and etorixocib (also compared to placebo + acetylsalicylic acid).|
The main study parameter is the difference in closure time (sec) as a measure of platelet aggregation. Closure time is measured by the Platelet Function Analyzer-100 (PFA-100). This apparatus measures the time needed for the blood to aggregate.
The difference calculated, is closure time of the addition of an NSAID to acetylsalicylic acid, versus closure time of acetylsalicylic acid and placebo within one subject.
|- Secondary outcome||N/A|
|- Timepoints||For each volunteer, the study consists of 3 cycles of 3 days during which 3 or 4 doses of study medication (2 or 3 x NSAID and 1 x acetylsalicylic acid) will be taken, and 2 medication-free wash out periods of 12 days. Total duration of the study for one volunteer is 33 days.
Volunteers are randomised in one of two groups. |
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||M.D., Phd H.E. Vonkeman|
|- CONTACT for SCIENTIFIC QUERIES|| M.E. Hoogh, de|
|- Sponsor/Initiator ||Medisch Spectrum Twente|
(Source(s) of Monetary or Material Support)
|Medisch Spectrum Twente|
|- Brief summary||While concern exists about the safety of the interaction between acetylsalicylic acid (prophylactic use) and NSAID's, observational research and intervention studies give conflicting results about this interaction. Because of the relatively safety of naproxen in cardiovascular disease compared to diclofenac it is interesting to look at the pharmacodynamic interaction between naproxen and ascetylsalicylic acid, to be able to advise about what is the best combination in a case the combination of acetylsalicylic acid and a NSAID is needed. Also there is a need to more closely look at this interaction with ibuprofen, meloxicam and etoricoxib, all often used in The Netherlands. |
|- Main changes (audit trail)|
|- RECORD||10-aug-2009 - 11-okt-2009|