Efficacy of Oral Paracetamol Compared With Oral Ketoprofen for Pain Management in Office Hysteroscopy: A Double-Blind Randomized Clinical Trial
Phase: PHASE4
Conditions: Office Hysteroscopy
Sponsor: Indonesia University

 
 
UNIVERSITAS INDONESIA 
 
 
EFFICACY OF  
ORAL PARACETAMOL COMPARED WITH ORAL KETOPROFEN FOR 
PAIN MANAGEMENT IN OFFICE HYSTEROSCOPY 
1ST VERSION JUNE 20TH 2020 
 
 
RESEARCH PROPOSAL 
Andika Widyatama 
 
SUPERVISOR: 
dr. Tricia Dewi Anggraeni, SpOG(K) 
Dr. dr. Vivian, Sp.FK, Ph.D 
 
 
RESIDENCY PROGRAM 
OBSTETRICS AND GYNECOLOGIST DEPARTMENT 
FACULTY OF MEDICINE UNIVERSITAS INDONESIA 
JAKARTA 
2019 
 

Study Protocol 
This study used a double-blind randomized clinical trial to assess the intensity of pain 
during the OH procedure and cramping within 30 minutes after the OH proce-dure in the 
group given paracetamol 1000 mg orally compared with ketoprofen 100 mg orally. This 
study also evaluated the side effects that occurred in both groups. This re-search was 
conducted at the OH clinic at RSUPN Dr. Cipto Mangunkusumo Kintani over a period of 
2 years. All patients who will undergo an OH procedure are checked for eligibility when 
they arrive and are offered to be research subjects if they meet the inclusion criteria, 
namely women who underwent an OH procedure and were not using analgesics in the 1 
month before joining the study. Individuals are not eligible if they have exclusion criteria, 
namely women with a history of asthma and women with a history of allergies to 
paracetamol or NSAID class drugs. Patients were given an ex-planation of the research 
procedures and asked for informed consent, if they were willing to take part in the 
research. This research was approved by the Health Research Ethics Committee of the 
Faculty of Medicine, Universitas Indonesia (ND – 0054/UN2.F1.DEPT.25/PDP.01/2022). 
Research subjects were divided into two groups. The first group received the an-algesic 
paracetamol tablet at a dose of 1000 mg orally and the second group received the 
analgesic ketoprofen tablet at a dose of 100 mg orally, each consisting of 30 subjects 
according to the sample size calculation formula. The total sample size of 60 patients (30 
per group) was determined based on previously published data and feasibility 
considerations. According to variability reported in comparable trials by Issat et al. (SD ≈ 
1.65) and Terán-Alonso et al. (SD ≈ 2.86), a group size of 30 participants per arm provides 
approximately 80% power (α = 0.05, two-sided) to detect a mean difference of about 1.2 
visual analogue scale (VAS) points under the lower-variance assumption (Issat et al.) or 
approximately 2.1 VAS points under a more conservative variance (Terán-Alonso et al.). 
[1, 2] Therefore, a total of 60 participants was considered a reasonable and practical 
compromise between statistical power and study feasibility. Subject allocation was 
carried out by block randomization so that an equal number of subjects were obtained in 
both groups. The block size was determined at 6 subjects. Randomization was carried 
out by computer and a randomization code was obtained by a research assistant. Then, 
the medicines are removed from each factory packaging, then put into sterile medicine 
plastic with serial numbers 1-60 which are kept by the nurse. The nurse handed over the 
medicine in the plastic according to the serial num-ber to the research subject patient 1 
hour before the OH procedure. Research subjects and researchers did not know the type 
of drug given (double blind). 
All OH procedures were performed using a Karl Storz Bettocchi Office Hyster-oscope 
(Germany) with an outer diameter of 3.5 mm. Vaginoscopy approach was ap-plied, 
without the use of a speculum or tenaculum. The uterine cavity was distended with 0.9% 
normal saline at a pressure of approximately 70 mmHg using a continuous flow system. 
No cervical preparation (such as misoprostol) was administered prior to the procedure. 
All procedures were conducted by the same experienced operator. 

The primary outcome of this study was the intensity of pain during the office 
hysteroscopy procedure, measured using a VAS at the time when the hysteroscope 
entered the external cervical ostium. The secondary outcomes included cramping pain 
within 30 minutes after the procedure, side effects associated with the administered 
analgesic, patient comfort, and the occurrence of vagal reflexes. 
Assessment of pain intensity during the procedure (when the hysteroscope in-strument 
enters the external cervical ostium) and cramping within 30 minutes after the OH 
procedure will use a VAS. Patients are asked to determine the VAS value in the 
questionnaire according to the intensity of pain and cramping they feel. Side effects of 
drug administration, comfort, and vagal reflexes will be assessed using the same ques-
tionnaire. 
 
 
 
Figure 1. Research Flow Diagram. 
 
References 
1. Issat, T.; Beta, J.; Nowicka, M.A.; Maciejewski, T.; Jakimiuk, A.J. A randomized, single-
blind, placebo-controlled trial for pain reduction during outpatient hysteroscopy after 
ketoprofen or intravaginal misoprostol. J Minim Invasive Gynecol. 2014; 21(6):921–927. 
2. Terán-Alonso, M.J.; Navarro-Gómez, M.; Rodríguez-Jiménez, B.; Pérez-González, M.; 
Abadía-Cuchí, N.; Bajo-Arenas, J. Evaluation of pain in office hysteroscopy with prior 
analgesic medication: A prospective randomized study. Eur J Obstet Gynecol Reprod 
Biol. 2014; 183:22–26. 
Randomization 
(double blind) 
Office Hysteroscopy patients  
(n = 60) 
Data analysis 
(n = 30) 
Paracetamol 1000 mg group 
(n = 30) 
Data analysis 
(n = 30) 
Ketoprofen 100 mg group  
(n = 30) 

Statistical Analysis Plan 
Data analysis was carried out using IBM SPSS version 25.0. Data distribution was 
assessed for normality. The age variable was normally distributed, while the procedure 
duration, VAS pain, cramping, and comfort scores were non-normally distributed. 
Between-group comparisons were originally analyzed using unpaired t-tests. Although 
several variables did not follow a normal distribution and non-parametric methods 
would have been more appropriate, the reported p-values remain unchanged, and all 
results were non-significant. Categorical data (such as side effects and vagal reflexes) 
were compared using Fisher’s exact test. Because only two treatment groups and a 
limited number of predefined outcomes were compared, no formal correction for 
multiple comparisons was applied.