Plain English Summary
Background and study aims
Hysterectomy is one of the most common operative gynecological procedures and states for surgical removal of the uterus. Rates of hysterectomy differ considerably between countries, ranging from a high of 5.4 per 1000 women in the USA to intermediate rates, such as 3.7 per 1000 in Italy to just 1.2 per 1000 in Norway. Total hysterectomy means removal of the whole uterus including cervix, subtotal hysterectomy states for the removal of uterus without cervix, preferred by some surgeons in order to decrease the negative effect on pelvic floor and sexual functions, however, this has not been confirmed. Indications for hysterectomy include menorrhagia as the most frequent indication in premenopausal women due to myomas or adenomyosis, pelvic pain due to endometriosis/adenomyosis after unsuccessful conservative treatment and uterine prolapse. Malignancy or postpartum hemorrhage account only for 10% of all hysterectomies. In general, hysterectomy improves psychological and general wellbeing of the patients due to removal of the symptoms that led to the surgery. However, patients quality of life during postoperative recovery is significantly impaired by symptoms such as fatigue, headache, nausea, depression, pain, wound infection, bleeding. These symptoms may have a significant social and economic impact. During surgery, biological pathways leading to oxidative stress and the production of free radicals are activated.
Despite many studies on the aspects of postoperative recovery, no consensus about a validated procedure to accelerate or assist recovery in this period exists.
Taking into account findings on the effect of an extract from the wood of French oak (Quercus robur), Robuvit® (further referred to as Robuvit), on energy level and mental health and the positive outcome of clinical studies related to improvement of symptoms of fatigue, burnout, recovery after sport or fatigue in medical convalescence all in conjunction with reduction of oxidative stress, we investigate the influence of Robuvit on recovery of women after hysterectomy.
Who can participate?
Women underwent hysterectomy for benign indications such as meno-/metrorrhagia or uterine prolapse can participate.
What does the study involve?
Patients are taking either Robuvit or placebo, whose effect will be compared. Patients are randomly and blindly divided into two arms (1:1 ratio) – Robuvit and placebo groups. Patients receive three times daily 100 mg Robuvit (300 mg/day) or 3 capsules placebo for 8 weeks. Placebo capsules were of the same shape and appearance as capsules containing Robuvit.
What are the possible benefits and risks of participating?
The improvement of recovery and post-operative state after the hysterectomy is expected after the intervention with Robuvit.
No adverse effects were seen after taking Robuvit In previous studies.
Where is the study run from?
The study is running in one centre: Department of II. Gynecology and Obstetrics, Medical Faculty, Comenius University and University hospital, Bratislava, Slovakia.
When is the study starting and how long is it expected to run for?
The study started in June 2014 and is expected to be completed in December 2019.
Who is funding the study?
The study is funded partly by Horphag Res., by University of Comensky and Mind and Health, civil association (in Slovak: Rozum a Zdravie, občianske združenie).
Who is the main contact?
Prof. Zdenka Durackova (zdenka.durackova@fmed.uniba.sk)
Trial website
Contact information
Type
Scientific
Primary contact
Prof Zdenka Ďuračková
ORCID ID
http://orcid.org/0000-0001-6956-7038
Contact details
Sasinkova 2
Bratislava
81372
Slovakia
+421259357564
zdenka.durackova@fmed.uniba.sk
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
N/A
Study information
Scientific title
The effect of Robuvit® on convalescence and healing process of women undergoing hysterectomy The effect of Robuvit® on convalescence and healing process of women undergoing a hysterectomy
Acronym
HyeRob
Study hypothesis
The recovery state of women after a hysterectomy may be positively affected by the use of Robuvit®.
Ethics approval
Approved 25/06/2014, Ethical Committee of the University Hospital and the Faculty of Medicine, Comenius University Bratislava, Slovakia (Pažitková 4, 821 01, Bratislava; +421 2 48 234 793; okf@ru.unb.sk), ref: 159/2014.
Study design
Single-centre, randomized, double blinded, placebo controlled interventional study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Quality of life
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Wellbeing and recovery of women after a hysterectomy
Intervention
Patients are randomly and blindly divided into two arms (1:1 ratio) – Robuvit and placebo groups. Robuvit® is a registered trademark of Horphag Research. Placebo contained magnesium stearate, silicon dioxide, stearic acid, glucidex 12D. In addition, light brown dye was added to yield the same appearance as the verum capsules. Robuvit and placebo capsules were provided by Horphag Res.
After vaginal hysterectomy, capsules are dispensed to patients starting on the third day postoperatively. Patients receive three times daily 100 mg Robuvit (300 mg / day) or 3 capsules placebo for 8 weeks. Placebo capsules were of the same shape and appearance as capsules containing Robuvit. The Technician, the patients, the physicians and the statistician, evaluating the results of the study, were blinded until the end of the statistical evaluation.
Intervention type
Drug
Phase
Not Specified
Drug names
Robuvit
Primary outcome measure
Mental and physical wellbeing is measured using validated standardized questionnaire SF-36 at the baseline (before surgery) and after weeks 4 and 8 of intervention.
Secondary outcome measures
1. Biochemical parameters (glucose, creatinine, uric acid, total proteins, triacylglycerols, total cholesterol, LDL- and HDL-cholesterols an hsCRP) are measured using standard biochemical procedures in Medirex servis, s.r.o. Bratislava at the baseline and after week 8 of intervention.
2. Markers of oxidative stress (markers of lipid damage - lipoperoxides, protein damage - AOPP, total antioxidant status as TEAC and on the activities and the levels of MMP-2 and MMP-9) are measured using the following methods:
2.1. The antioxidant capacity of plasma was determined with the TEAC method (trolox equivalent antioxidant capacity) on the Hitachi 911 automated analyser using the Randox set (United Kingdom). Antioxidant activity was expressed in nmol trolox/mL of plasma (Re et al., 1999).
2.2. Lipid hydroperoxides (LPx) in blood serum were determined according to El-Saadani et al. (1989), advanced oxidation protein products (AOPP) according to the modified Witko-Sarsat et al. (1998).
2.3. The gelatinolytic activities of metalloproteinases (MMPs) were analyzed in plasma by zymography in 10% polyacrylamide gels containing gelatin (Giannakos et al., 2019). Protein level of MMPs was determined by Western blot analysis (Bartekova et al., 2015).
2.4. Investigation of metabolites of Robuvit in serum/blood cells which should be formed in GIT from the original molecules present in Robuvit and determination of potential biological activities.
Overall trial start date
15/06/2014
Overall trial end date
30/06/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Undergoing hysterectomy for benign indications such as meno/metrorrhagia or uterine prolapse. Preoperatively, the patients did not take any analgesics or other drugs related to the symptomatology
2. Signed informed consent.
Participant type
Patient
Age group
Not Specified
Gender
Female
Target number of participants
60
Participant exclusion criteria
1. Currently enrolled in another study.
2. Malignant disease, severe systemic disease, chronic autoimmune diseases.
3. Significant psychiatric disorders or receiving antipsychotic drug.
Recruitment start date
01/02/2015
Recruitment end date
31/12/2017
Locations
Countries of recruitment
Slovakia
Trial participating centre
Comenius University and University Hospital
Department of II. Gynecology and Obstetrics
Medical Faculty
Ružinovská 61.
Bratislava
82606
Slovakia
Sponsor information
Organisation
Comenius University, Faculty of Medicine
Sponsor details
Špitálska 24
Bratislava
81372
Slovakia
+421 2 59357 466
dekan.sekretariat@fmed.uniba.sk
Sponsor type
Research organisation
Website
Funders
Funder type
Industry
Funder name
Horphag Research Ltd.
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The outcome of monitoring the impact of Robuvit on the recovery and well-being of women after hysterectomy will be published in 2019.
IPD sharing statement: the datasets generated during and/or analysed during the current study are/will be available upon request from responsible investigator Prof. Zdenka Ďuračková, PhD. (zdenka.durackova@fmed.uniba.sk ). Data will be available after the publishing of main results in accordance of study hypothesis. Patients in the Informed Consent were informed that all data on them are confidential. Their identity data will not be publicly available. If the results of this study are published, their personal data will remain confidential.
Intention to publish date
30/09/2019
Participant level data
Available on request
Basic results (scientific)
Publication list