PMID- 25299350
OWN - NLM
STAT- MEDLINE
DCOM- 20150702
LR  - 20181202
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 31
IP  - 1
DP  - 2015 Jan
TI  - A randomized study to compare the efficacy and safety of extended-release and 
      immediate-release tramadol HCl/acetaminophen in patients with acute pain 
      following total knee replacement.
PG  - 75-84
LID - 10.1185/03007995.2014.975338 [doi]
AB  - OBJECTIVE: To evaluate the relative efficacy and safety of extended-release 
      tramadol HCl 75 mg/acetaminophen 650 mg (TA-ER) and immediate-release tramadol 
      HCl 37.5 mg/acetaminophen 325 mg (TA-IR) for the treatment of moderate to severe 
      acute pain following total knee replacement. METHODS: This phase III, 
      double-blind, placebo-controlled, parallel-group study randomized 320 patients 
      with moderate to severe pain (>/=4 intensity on an 11 point numeric rating scale) 
      following total knee replacement arthroplasty to receive oral TA-ER (every 12 
      hours) or TA-IR (every 6 hours) over a period of 48 hours. In the primary 
      analysis, TA-ER was evaluated for efficacy non-inferior to that of TA-IR based on 
      the sum of pain intensity difference (SPID) at 48 hours after the first dose of 
      study drug (SPID48). Secondary endpoints included SPID at additional time points, 
      total pain relief at all on-therapy time points (TOTPAR), sum of SPID and TOTPAR 
      at all on-therapy time points (SPID + TOTPAR), use of rescue medication, 
      subjective pain assessment (PGIC, Patient Global Impression of Change), and 
      adverse events (AEs). RESULTS: Analysis of the primary efficacy endpoint (SPID48) 
      could not establish the non-inferiority of TA-ER to TA-IR. However, a post hoc 
      analysis with a re-defined non-inferiority margin did demonstrate the 
      non-inferiority of TA-ER to TA-IR. No statistically significant difference in 
      SPID at 6, 12, or 24 hours was observed between the TA-ER and TA-IR groups. 
      Similarly, analysis of TOTPAR showed that there were no significant differences 
      between groups at any on-therapy time point, and SPID + TOTPAR at 6 and 48 hours 
      were similar among groups. There was no difference in the mean frequency or 
      dosage of rescue medication required by both groups, and the majority of patients 
      in both the TA-ER and TA-IR groups rated their pain improvement as 'much' or 
      'somewhat better'. The overall incidence of >/=1 AEs was similar among the TA-ER 
      (88.8%) and TA-IR (89.5%) groups. The most commonly reported AEs by patients 
      treated with TA-ER and TA-IR included nausea (49.7% vs 44.4%), vomiting (28.0% vs 
      24.2%), and decreased hemoglobin (23.6% vs 26.1%). This study is limited by the 
      lack of placebo control, and the invalidity of the initial non-inferiority 
      margin. CONCLUSION: This study demonstrated that the analgesic effect of TA-ER is 
      non-inferior to TA-IR, and supports TA-ER as an effective and safe treatment for 
      moderate to severe acute pain post total knee replacement. CLINICAL TRIAL 
      REGISTRATION: Clinicaltrials.gov, NCT01814878.
FAU - Park, Yong-Beom
AU  - Park YB
AD  - Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine , Seoul , South Korea.
FAU - Ha, Chul-Won
AU  - Ha CW
FAU - Cho, Sung-Do
AU  - Cho SD
FAU - Lee, Myung-Chul
AU  - Lee MC
FAU - Lee, Ju-Hong
AU  - Lee JH
FAU - Seo, Seung-Suk
AU  - Seo SS
FAU - Kang, Seung-Baik
AU  - Kang SB
FAU - Kyung, Hee-Soo
AU  - Kyung HS
FAU - Choi, Choong-Hyeok
AU  - Choi CH
FAU - Chang, NaYoon
AU  - Chang N
FAU - Rhim, Hyou Young Helen
AU  - Rhim HY
FAU - Bin, Seong-Il
AU  - Bin SI
LA  - eng
SI  - ClinicalTrials.gov/NCT01814878
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20141031
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Combinations)
RN  - 0 (Ultracet)
RN  - 362O9ITL9D (Acetaminophen)
RN  - 39J1LGJ30J (Tramadol)
SB  - IM
MH  - Acetaminophen/*therapeutic use
MH  - Acute Pain/diagnosis/*drug therapy/etiology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Analgesics, Opioid/*therapeutic use
MH  - Arthroplasty, Replacement, Knee/*adverse effects
MH  - Delayed-Action Preparations
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Pain Measurement
MH  - Pain, Postoperative/diagnosis/*drug therapy/etiology
MH  - Tramadol/*therapeutic use
MH  - Treatment Outcome
MH  - Vomiting/chemically induced
OTO - NOTNLM
OT  - Acute pain
OT  - Pain intensity
OT  - Pain relief
OT  - Post-operative pain
EDAT- 2014/10/10 06:00
MHDA- 2015/07/03 06:00
CRDT- 2014/10/10 06:00
PHST- 2014/10/10 06:00 [entrez]
PHST- 2014/10/10 06:00 [pubmed]
PHST- 2015/07/03 06:00 [medline]
AID - 10.1185/03007995.2014.975338 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2015 Jan;31(1):75-84. doi: 10.1185/03007995.2014.975338. Epub 
      2014 Oct 31.