Jean Marty1, Dan Benhamou2, Dominique Chassard3, Nicole Emperaire4, Alain Roche5, Annick Mayaud6, Dominique Haro7, Xavier Baron8, Odile Hiesse-Provost9. 1. Department of Anesthesia Reanimation, Hôpital Beaujon, Clichy, France. 2. Department of Anesthesia Reanimation, Hôpital Antoine Béclère, Clamartt, France. 3. Department of Anesthesia Reanimation, Hôtel Dieu, Lyon, France. 4. Department ofAnesthesia Reanimation, Hôpital La Conception, Marseille, France. 5. Department ofAnesthesia Reanimation, Centre Hospitalier Universitaire, Saint André, Bordeaux, France. 6. Department of Anesthesia Reanimation, Centre Hospitalier de Caen, Caen,France. 7. Department of Anesthesia Reanimation, Clinique Mutualiste Eugène André,Lyon, France. 8. Department of Anesthesia Reanimation, Centre Hospitalier Saint Louis,La Rochelle, France. 9. Bristol-Myers Squibb Company, Rueil-Malmaison, France.
Abstract
BACKGROUND: Intravenous administration is the route of choice for drug therapy in the immediate postoperative period. Propacetamol (ProAPAP), an injectable prodrug of paracetamol requiring reconstitution, has demonstrated efficacy in managing acute pain and fever. However, it has been associated with pain at the injection site. A stable, ready-to-use formulation of paracetamol solution infused intravenously (IV-APAP) has been developed and might be associated with less pain at the injection site compared with ProAPAR. OBJECTIVE: The objective of this study was to assess the tolerability and efficacy of a single dose of IV APAP 1 g compared with those of a single dose of ProAPAP 2 g in patients with moderate to severe pain after minor gynecologic surgery. METHODS: This single-dose, randomized, double-blind, active-controlled,2-parallel-group study was conducted at 23 hospitals and outpatient clinics in France. After minor gynecologic surgery, patients reporting moderate to severe pain were randomized to receive a single 15-minute infusion of IV-APAP 1 g or ProAPAP 2 g (bioeyuivalent doses). Tolerability was monitored using local and systemic adverse event (AE) reporting, clinical examination including vital sign measurement, and patients' ratings of acceptability of the infusion. Efficacy end points included pain intensity at 0, 1, 2, 4, and 6 hours; median time to rescue medication (defined as the time at which 50% of patients requested rescue medication); and percentage of patients requesting rescue medication. Patients' satisfaction with the study drugs was assessed using patient's global evaluation (PGE) and the percentage of patients willing to receive the treatment again. RESULTS: Of the 163 women who were randomized, 161 received the studymedication. The IV-APAPgroup comprised 80 patients (mean [SD] age, 38.3 [12.8] years [range, 18.0-69.0 years]; mean [SD] weight, 61.1 [11.0] kg [range, 49.0-90.0 kg]), and the ProAPAP group comprised 81 patients (mean [SD] age, 33.9 [12.0] years [range, 18.0-67.0 years]; mean [SD] weight, 61.6 [10.2] kg [range, 42.0-95.5 kg]); the difference in mean age between the 2 groups was statistically significant (P < 0.05). The incidence of local treatment-emergent AEs (TEAEs) was significantly lower in the IV-APAP group compared with that in the ProAPAP group (7.5% vs 38.3%; P < 0.001). No between-group differences in the incidence of systemic TEAEs was found. All patients in the IV-APAP group found the infusion tolerable, compared with 95% of patients in the ProAPAP group. The median time to rescue medication was not evaluated because <50% of the patients in each group requested it. No significant differences in mean pain intensity score or percentage of patients requesting rescue medication were found between the 2 groups at any time point. The percentages of patients in the IV-APAP and ProAPAP groups who rated the study medication as good or excellent on the PGE (83.6% vs 75.6%; P < 0.05) and who were willing to receive the same treatment again (96.0% vs 81.0%; P = 0.005) were significantly higher with IV-APAP compared with ProAPAP. CONCLUSION: In these patients with moderate to severe pain after minor gynecologic surgery, a single dose of IV-APAP was associated with better local tolerability, similar analgesic efficacy, and greater patient satisfaction compared with a single bioequivalent dose of ProAPAP.
RCT Entities:
BACKGROUND: Intravenous administration is the route of choice for drug therapy in the immediate postoperative period. Propacetamol (ProAPAP), an injectable prodrug of paracetamol requiring reconstitution, has demonstrated efficacy in managing acute pain and fever. However, it has been associated with pain at the injection site. A stable, ready-to-use formulation of paracetamol solution infused intravenously (IV-APAP) has been developed and might be associated with less pain at the injection site compared with ProAPAR. OBJECTIVE: The objective of this study was to assess the tolerability and efficacy of a single dose of IV APAP 1 g compared with those of a single dose of ProAPAP 2 g in patients with moderate to severe pain after minor gynecologic surgery. METHODS: This single-dose, randomized, double-blind, active-controlled,2-parallel-group study was conducted at 23 hospitals and outpatient clinics in France. After minor gynecologic surgery, patients reporting moderate to severe pain were randomized to receive a single 15-minute infusion of IV-APAP 1 g or ProAPAP 2 g (bioeyuivalent doses). Tolerability was monitored using local and systemic adverse event (AE) reporting, clinical examination including vital sign measurement, and patients' ratings of acceptability of the infusion. Efficacy end points included pain intensity at 0, 1, 2, 4, and 6 hours; median time to rescue medication (defined as the time at which 50% of patients requested rescue medication); and percentage of patients requesting rescue medication. Patients' satisfaction with the study drugs was assessed using patient's global evaluation (PGE) and the percentage of patients willing to receive the treatment again. RESULTS: Of the 163 women who were randomized, 161 received the studymedication. The IV-APAP group comprised 80 patients (mean [SD] age, 38.3 [12.8] years [range, 18.0-69.0 years]; mean [SD] weight, 61.1 [11.0] kg [range, 49.0-90.0 kg]), and the ProAPAP group comprised 81 patients (mean [SD] age, 33.9 [12.0] years [range, 18.0-67.0 years]; mean [SD] weight, 61.6 [10.2] kg [range, 42.0-95.5 kg]); the difference in mean age between the 2 groups was statistically significant (P < 0.05). The incidence of local treatment-emergent AEs (TEAEs) was significantly lower in the IV-APAP group compared with that in the ProAPAP group (7.5% vs 38.3%; P < 0.001). No between-group differences in the incidence of systemic TEAEs was found. All patients in the IV-APAP group found the infusion tolerable, compared with 95% of patients in the ProAPAP group. The median time to rescue medication was not evaluated because <50% of the patients in each group requested it. No significant differences in mean pain intensity score or percentage of patients requesting rescue medication were found between the 2 groups at any time point. The percentages of patients in the IV-APAP and ProAPAP groups who rated the study medication as good or excellent on the PGE (83.6% vs 75.6%; P < 0.05) and who were willing to receive the same treatment again (96.0% vs 81.0%; P = 0.005) were significantly higher with IV-APAP compared with ProAPAP. CONCLUSION: In these patients with moderate to severe pain after minor gynecologic surgery, a single dose of IV-APAP was associated with better local tolerability, similar analgesic efficacy, and greater patient satisfaction compared with a single bioequivalent dose of ProAPAP.
Authors: Raymond S Sinatra; Jonathan S Jahr; Lowell W Reynolds; Eugene R Viscusi; Scott B Groudine; Catherine Payen-Champenois Journal: Anesthesiology Date: 2005-04 Impact factor: 7.892
Authors: B L Strom; J A Berlin; J L Kinman; P W Spitz; S Hennessy; H Feldman; S Kimmel; J L Carson Journal: JAMA Date: 1996-02-07 Impact factor: 56.272