Prevalence and Burden of Nausea and Vomiting in Pregnant Women in Switzerland: Survey Purity 2022

Nausea Clinical Trial

Official title:

Prevalence and Burden of Nausea and Vomiting in Pregnant Women in Switzerland: Survey Purity 2022

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06055192
• Other study ID #: OPEFF/0122/SU
• Status: Not yet recruiting
• Start date: September 2023
• Est. completion date: October 2024

Study information

• Verified date: September 2023
• Source: Effik SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The latest data on the prevalence of nausea in pregnancy in Switzerland is dated 2015 but has been hypothesised that the recent introduction on the market of new drugs against this symptom could modify its epidemiology. For this reason, we have planned the present survey, calculating an adequate sample size of Swiss pregnant women (the population of interest) and, according to a cross-sectional design, planning the collection of response variables with the aim of estimating the prevalence of burden and nausea and vomiting in pregnancy

Description:

Nausea with or without vomiting (Nausea and Vomiting in Pregnancy - NVP) in early pregnancy (before 9 and up to 16 weeks of gestation) is very common (50-80%); these symptoms rarely persist throughout pregnancy (10-20%). Even if NVP aetiology remains unknown, the cause is most likely multifactorial NVP severity can be assessed with the validated, 24-hour Pregnancy-Unique Quantification of Emesis (PUQE-24) Scale.

Management and treatment of NVP focus on reducing symptoms, improving quality of life, preventing serious complications, and minimising foetal effects of maternal pharmacologic treatment. It is advised to follow dietary and lifestyle recommendations, followed by available alternative and pharmacological treatments.

Swissmedic has recently approved doxylamine as a drug for the treatment of NVP symptoms in combination with pyridoxine (Cariban®, Effik SA, Switzerland). Its efficacy and safety have been widely studied. A 2014 data re-analysis of a previous meta-analysis took into account a total of 139414 women in reports about the safety of antihistamines and 129108 in reports about the safety of doxylamine. In these studies, 23485 women were exposed to antihistamines and 14624 were exposed to doxylamine. Neither increased foetal risk for congenital malformations nor other adverse pregnancy outcomes were demonstrated. The safety of the drug is additionally supported by extensive international literature.

Moreover, a recent study showed that Cariban® behaves as a prolonged-release formulation, which correlates with rapid absorption and arising of the actives in the plasma, but also long-lasting and sustained bioavailability, especially when administered following the complete posology. These results would underlie its demonstrated efficacy to relieve nausea and vomiting of pregnancy (NVP) under clinical settings.

The exposure to doxylamine-pyridoxine in pregnancy (or to the combination of doxylamine and pyridoxine) is classified as safe, and its use is recommended as first-line therapy of nausea and vomiting in pregnancy by the American College of Obstetricians and Gynaecologists (ACOG) Guidelines, by the Society of Obstetricians and Gynecologists of Canada and organizations such as Mother to Baby (formerly known as Organization of Teratogen Information Services.

An epidemiological study, published in 2015, stated that the prevalence of nausea in Switzerland was 70,6%. It is to be noted that women who reported nausea also had a high burden of co-morbidity, especially heartburn and reflux symptoms and an association of NPV with symptoms of depression and sick leave was shown.

It is possible that the recent introduction of an association of doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg (Cariban®, Effik SA Switzerland) on the Swiss market and the recent publication of the SGGG Expert letter on NVP and hyperemesis gravidarum (1) could have had a substantial impact on the extent of this disturbance, the awareness of the therapists and the perception of the women.

In this context, a Survey will be carried out. A Survey is a procedure which, through a scientific method of detection (a questionnaire to be submitted to a representative sample of subjects related to the issue of the research) allows to collect, and subsequently to analyse, the data to study the relationships between different variables would yield significant scientific results.

The objectives of the study are: Evaluate the prevalence and burden that the symptoms of nausea and vomiting have in pregnant women in Switzerland.

The following outcomes will be evaluated:

• Demographic data (including ethnicity: Caucasian, African, Asian, or Other).

• NVP prevalence.

• Percentage of mild, medium, and severe cases based on PUQE-24.

• Percentage of answer allocation to NVP related questions.

• Onset for each symptom and its duration.

• Correlations between demographic data (age, first pregnancy status, multiparity, geographical origin, kinds of work and educational qualification) and the presence of symptoms and their severity.

• Correlation of the above-mentioned parameters with the use of non-pharmacological, pharmacological or both therapies.

• Analysis of drug therapies, of their correlation with the severity of the symptoms during pregnancy and with the possible outcomes of the same.

• Correlation between the severity of the symptoms and the consequences on the woman's personal life (family, work, etc.).

• Number of cases with hospitalization in relation to total and severity of symptoms (PUQE-24).

• Correlation between symptoms in pregnancy and outcomes based on data from the post pregnancy questionnaire (weight of the new-born, gestational age at birth and any complications).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: October 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects will be eligible for inclusion if all the following criteria are respected:

• Women aged = 18 years.

• Women in physiological pregnancy and between the 18th and 22nd week of pregnancy (at time of morphological ultrasound).

• Women able to communicate adequately with the Investigator and able to read, understand and provide the answers required by the questionnaires in one of the languages in which they will be provided (Italian, German, French or English).

• Women able to understand and who can provide valid informed consent to the Survey.

Exclusion Criteria:

• Subjects fulfilling one or more of the following exclusion criteria will not be included in the study:

• Twin pregnancy.

• Medically assisted procreation (MAP).

Related Conditions & MeSH terms

• Nausea
• Vomiting
• Vomiting of Pregnancy

Intervention

Other:
• Survey
Survey

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Effik SA	Opera CRO, a TIGERMED Group Company

References & Publications (42)

APGO. APGO. Nausea and vomiting of pregnancy. APGO Educational series on women's health issues. Boston: Jespersen & Associates, LLC; 2013. 2013.

Arsenault MY, Lane CA, MacKinnon CJ, Bartellas E, Cargill YM, Klein MC, Martel MJ, Sprague AE, Wilson AK. The management of nausea and vomiting of pregnancy. J Obstet Gynaecol Can. 2002 Oct;24(10):817-31; quiz 832-3. English, French. — View Citation

Berard A, Sheehy O, Gorgui J, Zhao JP, Soares de Moura C, Bernatsky S. New evidence for concern over the risk of birth defects from medications for nausea and vomitting of pregnancy. J Clin Epidemiol. 2019 Dec;116:39-48. doi: 10.1016/j.jclinepi.2019.07.014. Epub 2019 Jul 26. — View Citation

Biffi A, Rea F, Locatelli A, Cetin I, Filippelli A, Corrao G. Misleading meta-analyses of observational studies may generate unjustified alarms: The case of medications for nausea and vomiting in pregnancy. Pharmacol Res. 2021 Jan;163:105229. doi: 10.1016/j.phrs.2020.105229. Epub 2020 Oct 5. — View Citation

Brent RL. Bendectin: review of the medical literature of a comprehensively studied human nonteratogen and the most prevalent tortogen-litigen. Reprod Toxicol. 1995 Jul-Aug;9(4):337-49. doi: 10.1016/0890-6238(95)00020-b. — View Citation

Brott NR, Reddivari AKR. Doxylamine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Jun 22]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK551646/

Chin JW, Gregor S, Persaud N. Re-analysis of safety data supporting doxylamine use for nausea and vomiting of pregnancy. Am J Perinatol. 2014 Sep;31(8):701-10. doi: 10.1055/s-0033-1358772. Epub 2013 Dec 9. — View Citation

Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018 Jan;131(1):e15-e30. doi: 10.1097/AOG.0000000000002456. — View Citation

de Tejada BM, Vonzun L, Mandach DUV, Burch A, Yaron M, Hodel M, et al. Nausea and Vomiting of Pregnancy, Hyperemesis gravidarum. :5.

Doxylamine/pyridoxine for nausea and vomiting in pregnancy. Drug Ther Bull. 2019 Mar;57(3):38-41. doi: 10.1136/dtb.2018.000053. Epub 2019 Jan 31. No abstract available. — View Citation

Ebrahimi N, Maltepe C, Bournissen FG, Koren G. Nausea and vomiting of pregnancy: using the 24-hour Pregnancy-Unique Quantification of Emesis (PUQE-24) scale. J Obstet Gynaecol Can. 2009 Sep;31(9):803-807. doi: 10.1016/S1701-2163(16)34298-0. — View Citation

Einarson TR, Leeder JS, Koren G. A method for meta-analysis of epidemiological studies. Drug Intell Clin Pharm. 1988 Oct;22(10):813-24. doi: 10.1177/106002808802201021. — View Citation

fedlex-data-admin-ch-eli-cc-2013-643-20140101-en-pdf-a.pdf [Internet]. [cited 2022 Jun 13]. Available from: https://fedlex.data.admin.ch/filestore/fedlex.data.admin.ch/eli/cc/2013/643/20140101/en/pdf-a/fedlex-data-admin-ch-eli-cc-2013-643-20140101-en-pdf-a.pdf

Fejzo MS, Trovik J, Grooten IJ, Sridharan K, Roseboom TJ, Vikanes A, Painter RC, Mullin PM. Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nat Rev Dis Primers. 2019 Sep 12;5(1):62. doi: 10.1038/s41572-019-0110-3. — View Citation

Gilboa SM, Ailes EC, Rai RP, Anderson JA, Honein MA. Antihistamines and birth defects: a systematic review of the literature. Expert Opin Drug Saf. 2014 Dec;13(12):1667-98. doi: 10.1517/14740338.2014.970164. Epub 2014 Oct 11. — View Citation

Heitmann K, Holst L, Lupattelli A, Maltepe C, Nordeng H. Treatment of nausea in pregnancy: a cross-sectional multinational web-based study of pregnant women and new mothers. BMC Pregnancy Childbirth. 2015 Dec 1;15:321. doi: 10.1186/s12884-015-0746-2. — View Citation

Heitmann K, Nordeng H, Havnen GC, Solheimsnes A, Holst L. The burden of nausea and vomiting during pregnancy: severe impacts on quality of life, daily life functioning and willingness to become pregnant again - results from a cross-sectional study. BMC Pregnancy Childbirth. 2017 Feb 28;17(1):75. doi: 10.1186/s12884-017-1249-0. — View Citation

Heitmann K, Solheimsnes A, Havnen GC, Nordeng H, Holst L. Treatment of nausea and vomiting during pregnancy -a cross-sectional study among 712 Norwegian women. Eur J Clin Pharmacol. 2016 May;72(5):593-604. doi: 10.1007/s00228-016-2012-6. Epub 2016 Jan 27. — View Citation

Koren G, Boskovic R, Hard M, Maltepe C, Navioz Y, Einarson A. Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding):S228-31. doi: 10.1067/mob.2002.123054. — View Citation

Koren G, Clark S, Hankins GD, Caritis SN, Miodovnik M, Umans JG, Mattison DR. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010 Dec;203(6):571.e1-7. doi: 10.1016/j.ajog.2010.07.030. Epub 2010 Sep 16. — View Citation

Koren G, Cohen R. Measuring the severity of nausea and vomiting of pregnancy; a 20-year perspective on the use of the pregnancy-unique quantification of emesis (PUQE). J Obstet Gynaecol. 2021 Apr;41(3):335-339. doi: 10.1080/01443615.2020.1787968. Epub 2020 Aug 19. — View Citation

Koren G. Safety considerations surrounding use of treatment options for nausea and vomiting in pregnancy. Expert Opin Drug Saf. 2017 Nov;16(11):1227-1234. doi: 10.1080/14740338.2017.1361403. Epub 2017 Aug 9. — View Citation

Lee J, Einarson A, Gallo M, Okotore B, Koren G. Longitudinal change in the treatment of nausea and vomiting of pregnancy in Ontario. Can J Clin Pharmacol. 2000 Winter;7(4):205-8. — View Citation

Lee NM, Saha S. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am. 2011 Jun;40(2):309-34, vii. doi: 10.1016/j.gtc.2011.03.009. — View Citation

London V, Grube S, Sherer DM, Abulafia O. Hyperemesis Gravidarum: A Review of Recent Literature. Pharmacology. 2017;100(3-4):161-171. doi: 10.1159/000477853. Epub 2017 Jun 23. — View Citation

Madjunkova S, Maltepe C, Koren G. The delayed-release combination of doxylamine and pyridoxine (Diclegis(R)/Diclectin (R)) for the treatment of nausea and vomiting of pregnancy. Paediatr Drugs. 2014 Jun;16(3):199-211. doi: 10.1007/s40272-014-0065-5. — View Citation

Madjunkova S, Maltepe C, Koren G. The Leading Concerns of American Women with Nausea and Vomiting of Pregnancy Calling Motherisk NVP Helpline. Obstet Gynecol Int. 2013;2013:752980. doi: 10.1155/2013/752980. Epub 2013 Apr 15. — View Citation

McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies. Teratology. 1994 Jul;50(1):27-37. doi: 10.1002/tera.1420500105. — View Citation

McParlin C, O'Donnell A, Robson SC, Beyer F, Moloney E, Bryant A, Bradley J, Muirhead CR, Nelson-Piercy C, Newbury-Birch D, Norman J, Shaw C, Simpson E, Swallow B, Yates L, Vale L. Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA. 2016 Oct 4;316(13):1392-1401. doi: 10.1001/jama.2016.14337. — View Citation

Nausea and Vomiting of Pregnancy (NVP). 2022;

Neutel CI, Johansen HL. Measuring drug effectiveness by default: the case of Bendectin. Can J Public Health. 1995 Jan-Feb;86(1):66-70. — View Citation

Nuangchamnong N, Niebyl J. Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of nausea and vomiting in pregnancy: an overview. Int J Womens Health. 2014 Apr 12;6:401-9. doi: 10.2147/IJWH.S46653. eCollection 2014. — View Citation

Office FS. Births [Internet]. [cited 2022 Jun 14]. Available from: https://www.bfs.admin.ch/bfs/en/home/statistiken/bevoelkerung/geburten-todesfaelle/geburten.html

Persaud N, Chin J, Walker M. Should doxylamine-pyridoxine be used for nausea and vomiting of pregnancy? J Obstet Gynaecol Can. 2014 Apr;36(4):343-348. doi: 10.1016/S1701-2163(15)30611-3. — View Citation

Rubenfeld GD. Surveys: an introduction. Respir Care. 2004 Oct;49(10):1181-5. — View Citation

Safdar N, Abbo LM, Knobloch MJ, Seo SK. Research Methods in Healthcare Epidemiology: Survey and Qualitative Research. Infect Control Hosp Epidemiol. 2016 Nov;37(11):1272-1277. doi: 10.1017/ice.2016.171. Epub 2016 Aug 12. — View Citation

Saz-Leal P, Zamorano-Dominguez L, Frias J, Guerra P, Saura-Valls M, Roca-Juanes R, Nebot-Troyano J, Garcia-Aguilar E, Vilchez T, Urso K. Bioavailability of Cariban(R) Capsules: A Modified-Release Fixed-Dose Combination of Doxylamine and Pyridoxine to Relieve Nausea and Vomiting During Pregnancy. Drugs R D. 2023 Jun;23(2):185-195. doi: 10.1007/s40268-023-00425-7. Epub 2023 Jun 15. — View Citation

Seto A, Einarson T, Koren G. Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis. Am J Perinatol. 1997 Mar;14(3):119-24. doi: 10.1055/s-2007-994110. — View Citation

Smolina K, Hanley GE, Mintzes B, Oberlander TF, Morgan S. Trends and Determinants of Prescription Drug Use during Pregnancy and Postpartum in British Columbia, 2002-2011: A Population-Based Cohort Study. PLoS One. 2015 May 26;10(5):e0128312. doi: 10.1371/journal.pone.0128312. eCollection 2015. — View Citation

SR 810.301 - Ordinance of 20 September 2013 on Human Research with the Exception of Clinical Trials (Human Research Ordinance, HRO) [Internet]. [cited 2022 Jun 13]. Available from: https://www.fedlex.admin.ch/eli/cc/2013/642/en

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008 Apr;61(4):344-9. doi: 10.1016/j.jclinepi.2007.11.008. — View Citation

WMA - The World Medical Association-WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects [Internet]. [cited 2022 Jun 13]. Available from: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/

* Note: There are 42 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Outcome Measure	Evaluate the prevalence and burden that the symptoms of nausea and vomiting have in pregnant women in Switzerland	185 days
Secondary	Secondary Outcome Measure	demographic data (including ethnicity: Caucasian, African, Asian or Other).	185 days
Secondary	Secondary Outcome Measure	NVP prevalence	185 days
Secondary	Secondary Outcome Measure	Percentage of mild, medium, and severe cases based on PUQE-24.	185 days
Secondary	Secondary Outcome Measure	Percentage of answer allocation to NVP related questions	185 days
Secondary	Secondary Outcome Measure	Onset for each symptom and its duration	185 days
Secondary	Secondary Outcome Measure	Correlations between demographic data (age, first pregnancy status, multiparity, geographical origin, kinds of work and educational qualification) and the presence of symptoms and their severity.	185 days
Secondary	Secondary Outcome Measure	Correlation of the above-mentioned parameters with the use of non-pharmacological, pharmacological (e.g., Cariban®) or both therapies.	185 days
Secondary	Secondary Outcome Measure	Analysis of drug therapies, their correlation with the severity of the symptoms during pregnancy and with the possible outcomes of the same	185 days
Secondary	Secondary Outcome Measure	Correlation between the severity of the symptoms and the consequences on the woman's personal life (family, work, etc.).	185 days
Secondary	Secondary Outcome Measure	Number of cases with hospitalization in relation to total and severity of symptoms (PUQE-24).	185 days
Secondary	Secondary Outcome Measure	Correlation between symptoms in pregnancy and outcomes based on data from the post pregnancy questionnaire (weight of the new-born, gestational age at birth and any complications).	185 days