Clinical Studies

In US studies, 929 patients received RAPLON^™ (rapacuronium bromide) for Injection including 219 pediatric, 146 geriatric, and 20 obstetric patients. In European studies, 964 patients received RAPLON^™ including 165 pediatric and 63 geriatric patients. The majority of patients, 91%, were ASA (American Society of Anesthesiologists) Class I or II, approximately 8% were ASA Class III, and approximately 1% were ASA Class IV.

Neuromuscular function parameters following administration of RAPLON^™, succinylcholine, and mivacurium were compared in one clinical study. In direct comparison with succinylcholine and mivacurium, RAPLON^™ at the recommended 1.5 mg/kg dose had a mean (SD) onset of action of 98 (46) seconds compared with 67 (27) seconds for succinylcholine and 127 (50) seconds for mivacurium. RAPLON^™ had a mean (SD) clinical duration of 15 (6) minutes compared with 9 (3) minutes for succinylcholine and 21 (5) minutes for mivacurium. Table 13 presents these neuromuscular function parameters in patients 18 years of age and older.

TABLE 13: Neuromuscular Function Parameters Following an Initial Dose of RAPLON^™, Succinylcholine, or Mivacurium in Adults (ł18 years)

Drug/ Dosage	Time to Maximum Block^a(sec)	Maximum Block^b (%)	Clinical Duration^c (min)	25–75% T₁ Recovery Index(min)	Time to 70% T₄/T₁Recovery^d (min)
RAPLON^™ 1.5 mg/kg
n	28	28	25	22	16
Mean (SD)	98 (46)	99 (2)	15 (6)	8 (5)	38 (21)
Range	35–219	94–100	7–30	2–21	21–101
Succinylcholine 1 mg/kg
n	30	30	29	29	N/A
Mean (SD)	67 (27)	99 (2)	9 (3)	2 (1)
Range	31–138	90–100	5–15	1–4
Mivacurium 0.25 mg/kg^e
n	25	25	21	24	18
Mean (SD)	127 (50)	100 (0.4)	21 (5)	9 (4)	32 (7)
Range	64–261	99–100	14–29	4–20	22–45

a=Time from injection to maximum block (peak effect)

b=100 – % T₁ control at peak effect)

c=Time from injection to return to 25% of control T₁

d=Time from injection to recovery of 70% T₄/T₁

e=Administered as a divided dose (0.15 mg/kg followed in 30 sec by 0.10 mg/kg), parameter measured from second dose

Intubating conditions following administration of RAPLON^™ and succinylcholine were compared in three randomized, multicenter trials conducted in the US, France, and Germany. A blinded rater assessed intubating conditions on the Viby-Mogensen scale (see Table 14) 50 seconds after administration of the neuromuscular blocking agent. Several different anesthetic techniques were used. In the US study, fentanyl was given about 5 minutes before intubation followed by propofol one to two minutes before intubation. The French study was similar except that thiopental was used instead of propofol. The German study tested a rapid sequence, with initiation of administration of the neuromuscular blocking agent within a few seconds after the end of the injection of the hypnotic, either fentanyl and thiopental or alfentanil and propofol were used at random. Tables 15 and 16 show the intubation scores in adults (18 to 64 years) and in geriatric patients (ł65 years).

TABLE 14: Viby-Mogensen Scale

	CLINICALLY ACCEPTABLE
	Excellent^†	Good^†	Poor^†
Vocal Cord Position	Abducted	Intermediate	Closed
Vocal Cord Movement	None	Moving	Closing
Easiness of Laryngoscopy^*	Easy	Fair	Difficult
Airway Reaction	None	Diaphragm	Sustained >10sec
Movement of Limbs	None	Slight	Vigorous

^* Easy: Jaw relaxed; no resistance

Fair: Jaw relaxed; slight resistance

^† Excellent: All items excellent

Good: All items excellent or good

Poor: Any item poor

Intubating dosages of 1.5 and 2.5 mg/kg of RAPLON^™ were evaluated in 784 patients. A population of patients undergoing Cesarean section was also studied (see below).

TABLE 15: Intubation Scores in Adults (18 to 64 years) With Laryngoscopy Initiated at 50 Seconds Following Administration of RAPLON^™ or Succinylcholine

Study	US		France		Germany
Drug/Dosage	RAPLON^™ 1.5 mg/kg n=124	Succinyl- choline 1.0 mg/kg n=112	RAPLON^™ 1.5 mg/kg n=128	Succinyl- choline 1.0 mg/kg n=128	RAPLON^™ 1.5 mg/kg n=160	Succinyl- choline 1.0 mg/kg n=166
Excellent Good Poor Impossible	43% 44% 13% 0%	67% 29% 4% 2%	30% 55% 9% 5%	48% 41% 9% 2%	51% 39% 11% 0%	73% 24% 3% 0%

TABLE 16: Intubation Scores in Geriatric Patients (ł65 years) With Laryngoscopy Initiated at 50 Seconds After Administration of RAPLON^™ or Succinylcholine

Study	US		France
Drug/Dosage	RAPLON^™ 1.5 mg/kg n=26	Succinylcholine 1.0 mg/kg n=28	RAPLON™ 1.5 mg/kg n=25	Succinylcholine 1.0 mg/kg n=26
Excellent Good Poor Impossible	50% 46% 4% 0%	79% 21% 0% 0%	32% 48% 4% 16%	62% 35% 0% 4%

Source:
http://www.rapacuronium.com/insert.htm