Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03250494 |
| Other study ID # |
17585 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
August 11, 2017 |
| Last updated |
August 11, 2017 |
| Start date |
December 2014 |
| Est. completion date |
January 2016 |
Study information
| Verified date |
August 2017 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
75 female patients were randomly allocated into one of three equal groups. Group I(GI)
received Dulox 60 mg orally and 100 ml 0.9% sodium chloride solution (NS) intravenous
infusion (IVI) over 15 min, group II(GII): received combined Dulox capsule 60 mg orally and
Dex 0.1mg/kg mixed with 100 ml NS IVI and group III(GIII) received identical placebo
duloxetine capsule and 100 ml NS IVI as a placebo for Dex, 2 hours preoperatively. Patients`
vitals, VAS and sedation score were assessed at 30 minutes, 1h, 2 h, 6h and 12h
postoperatively. Total pethidine requirements, plasma cortisol, PONV and patient`s
satisfaction were recorded.
Description:
This study was designed to be a randomized, placebo-controlled, double-blinded parallel study
and this study was carried out at Ain-Shams university hospitals, from December 2014 to
January2016, on 75 female patients aged between 25 and 35 years old of the American Society
of Anesthesiologists (ASA) physical status I and II scheduled for elective laparoscopic
gynecological surgeries (for infertility) under general anesthesia. Approval was obtained
from the institutional ethical committee and written informed consent was obtained from all
patients.
Patients were not admitted to the study if any of the following criteria were present: (1)
patient`s refusal, (2) duration of surgery more than 90 minutes, (3) allergy to any drugs of
the study, (4) smokers, history of drug or alcohol abuse, (5) treatment with antidepressants,
(6) history of diabetes or epilepsy, (7) , history of chronic pain or daily intake of
analgesics within 24 h before surgery, (8) treatment with systemic glucocorticoids within 4
weeks before surgery and (9) impaired kidney or liver functions.
Patients were randomly allocated into 3 equal groups, group (I) (GI) (n=25) each patient
received Dulox capsule (60mg) orally with sips of water 2 hours preoperatively and 100 ml
0.9% sodium chloride solution (NS) intravenous infusion (IVI) over 15 min (Placebo), group
(II) (GII) (n=25) each patient received combined Dulox capsule (60 mg) orally with sips of
water and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI over 15 min, 2 hours preoperatively and
group (III) (GIII) (control group) (n=25) each patient received a placebo capsule identical
to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone 2 hours
preoperatively. Dulox was presented as CYMBALTA® capsules manufactured by Lilly del Caribe
Inc. Imported by Elco and Dex was presented as dexamethasone sulphate ampoules 8mg in 2ml.
(Medical Union Pharmaceutical, Egypt MUP). Randomization was done using computer-generated
number table of random numbers in a 1:1 ratio and conducted using sequentially numbered,
opaque and sealed envelope (SNOSE). Active Dulox capsules were indistinguishable from placebo
capsules and placebo capsules contained starch. The study drugs were prepared by the hospital
pharmacy and follow-up of patients was conducted by the anesthesia residents not involved in
any other part of the study.
During the preoperative anesthetic evaluation, patients were familiarized with 10 cm marked
visual analogue scale (VAS) for PO assessment of pain, where 0 cm defines no pain and 10 cm
defines the maximum intolerable pain. Patients were also assured that they would receive
intramuscular injection (IM) of pethidine 0.5 mg / kg once they experienced pain
postoperatively (patients with (VAS > 3).
The general anesthesia technique was standardized for all the patients as well as monitors
including 5 lead ECG, non- invasive blood pressure (NIBP) monitor, pulse oximetry and
capnography after intubation using Datascope monitors. Neuromuscular function was monitored
using a peripheral nerve stimulator. After establishing an intravenous (IV) line, induction
of general anesthesia with fentanyl (2 ug/kg) and sleeping dose of propofol followed by
rocuronium (0.6 mg/kg) to facilitate orotracheal intubation was done. Anesthesia was
maintained using isoflurane in oxygen and air. Ranitidine (50 mg/ampoule) was given diluted
in 10 ml 0.9% sodium chloride solution (NS) slowly (IV) over 10 minutes as a gastroprotective
regimen. At the end of the surgery, the residual neuromuscular paralysis was antagonized with
neostigmine (0.05 mg/kg) and atropine (0.01 mg/kg). After satisfactory recovery, patients
were extubated and transferred to the post-anesthesia care unit (PACU) where they were
monitored with ECG, NIBP and pulse oximetry.
Assessment of patients` vitals (HR, MAP), arterial SpO2, sedation score, visual analog scale
(VAS), the first analgesic requirement time and adverse effects (e.g. nausea, vomiting
(PONV), pruritis) were done at 30 minutes, 1h, 2 h, 6h and 12h postoperatively.
PO pain was evaluated at rest based on visual analogue scale, first time to ask for rescue
analgesia and total pethidine requirements in 12 hours (mg) postoperatively were recorded.
Assessment of sedation was according to sedation score (Ramsay sedation scale) (14).
Hypotension was considered if there was 20% decrease below the baseline for MAP and was
treated with IV bolus of ephedrine (3-6 mg). Bradycardia was considered if the heart rate <
55 beats/min and was treated with IV atropine (0.01mg/kg). Respiratory depression was defined
as a respiratory rate less than 10 breaths/min-1 or peripheral oxygen saturation less than
95% and was treated with oxygen through a transparent face mask and the intermittent doses of
IV naloxone (0.4 mg). IV granisetron (1mg) was given in case of vomiting or after 2
successive episodes of nausea. Pruritus was evaluated with a 4-point scale (0=absent, 1=mild,
2=moderate, 3=severe or requiring treatment), and patients with severe pruritus were treated
with IV clemastine (TavegylR) (2 mg / ampoule).
Patient`s satisfaction was done by asking the patient to answer the question, 'How would you
rate your experience after the surgery?' using a 7-point Likert verbal rating scale (15) and
acceptable satisfaction score of the patient being 5-7.
Hormonal stress response was assessed through recording plasma cortisol (micrograms / dl) 2
hours postoperatively. Serum cortisol was measured by a Fluorescence Polarization Immunoassay
Technology (FPIA) by the Abbott AXSYM system with the following reference ranges (morning
serum cortisol 4.2-38.4 ug/dl) and evening serum cortisol 1.7-16.6 ug/dl).
