Clinical Trial: Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: The CLONEMESI Study: a Randomized Placebo-controlled Study With Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum.
Brief Summary: CLONEMESI is an academic, independent, randomized placebo-controlled trial to assess the effect of transdermal (TD) clonidine in improving the symptoms of severe Hyperemesis Gravidarum(HG) affecting women in their 6th-12th week of pregnancy. The study has a crossover design.
Detailed Summary:
Setting. The trial is performed at a single hospital setting after admission of patients.
Ethics. The study has been approved by our local Ethics Committee and women are requested to sign an informed consent. No pharmaceutical company is involved in any phases of the trial including protocol design, study conduction, coordination and monitoring, data handling and analysis.
Randomization. The patients are allocated to a random list to receive first placebo and then TD clonidine or the other way round.
Blinding. Neither the patients nor their attending caregivers know the order of administration . The outcome assessors are blinded as well.
Treatment.The patients are randomly treated with and without TD clonidine for 2 consecutive periods of 5 days , other antiemetic drugs (promethazine, metoclopramide, ondansetron) and anti- reflux drugs (ranitidine, omeprazole) being administered on a scheduled or as-needed basis. All patients receive intravenous hydration and supplementation with thiamine.
Assessment. Physical condition of patients are assessed daily: blood pressure (lying and standing), body weight, morning ketonuria. Two different clinical self administered scores as PUQE (Pregnancy Unique Quantification of Emesis) and VAS (Visual Analogue Scale) are employed to check daily the intensity of symptoms and the sense of wellbeing. The consumption of antiemetic and anti-reflux drugs administered in the two periods is monitored .
Sponsor: Azienda Ospedaliera Città della Salute e della Scienza di Torino
Current Primary Outcome:
- PUQE Score for Assessment of Severity in Hyperemesis Gravidarum [ Time Frame: Mean values of first period of five days are compared with mean values of second period of five days. Change is reported as baseline value - value at day 5 or at day 10. ]
PUQE in an acronym for Pregnancy Unique Quantification of Emesis, a validated clinical score for assessment of severity of emesis in pregnancy.
It is composed of three items; every item has a score from 1 (best) to 5 (worst).
The sum range varies from 3 (best) to 15 (worst). Participants are followed for the whole duration of hospital stay (10 days) asking them to score their symptoms daily.
- VAS Score for Assessment of Severity in Hyperemesis Gravidarum [ Time Frame: Mean values of first period of five days are compared with mean values of second period of five days. Change is reported as baseline value - value at day 5 or at day 10. ]VAS is a Visual Analogic Scale formulated in 5 items. Every item has a score from 0 (best) to 10 (worst). The sum range swings from 0 (best ) to 50 (worst). Participants are followed for the whole duration of hospital stay (10 days) asking them to score their symptoms daily.
Original Primary Outcome:
- PUQE Score for Assessment of Severity in Hyperemesis Gravidarum [ Time Frame: change from baseline at 5 days and at 10 days ]
PUQE in an acronym for Pregnancy Unique Quantification of Emesis, the only validated clinical score for assessment of severity of emesis. The range varies from 3 (best) to 15 (worst).
Participants will be followed for the whole duration of hospital stay (10 days) comparing the change from baseline in first period of 5 days with the second of 5 days
- VAS Score for Assessment of Severity in Hyperemesis Gravidarum [ Time Frame: change from baseline at 5 days and at 10 days ]
VAS is a Visual Analogic Scale formulated of 5 items. The range swings from 0 (best ) to 50 (worst).
Participants will be followed for the whole duration of hospital stay (10 days) comparing the first period of 5 days with second of 5 days
Current Secondary Outcome:
- Morning Urine Ketonuria [ Time Frame: participants are followed for the whole duration of hospital stay (10 days) comparing the first period of 5 days with the second period of 5 days ]Morning urine ketonuria is a simple direct marker of starving associated to nausea and vomiting
- Daily Doses of Standard Antiemetic Drugs Required in the Two Different Periods. [ Time Frame: participants are followed for the whole duration of hospital stay (10 days) comparing the first period of 5 days with the second period of 5 days ]
The patients were randomly treated with and without TD clonidine (5mg patch) for 2 consecutive periods of 5 days , other antiemetic drugs (promethazine, prochlorperazine, metoclopramide, ondansetron) and anti reflux drugs (ranitidine, omeprazole) being administered on a scheduled or as-needed basis.
All patients received intravenous hydration and supplementation with thiamine, during both periods. The use of steroids was allowed as a rescue medication in case of further worsening of symptoms.
- Number of Days Off i.v. Therapy, the TD System (Clonidine/Placebo) Being Applied Only [ Time Frame: participants are followed for the whole duration of hospital stay (10 days) comparing the first period of 5 days with the second period of 5 days ]if the symptoms improve the patient and her doctors may decide to stop parenteral drugs continuing the TD system therapy.
- Number of Patients Choosing Active Treatment for Off-label, Compassionate Use. [ Time Frame: at 10 days since start of treatment ]the patients were asked to choose between two transdermal systems (active drug versus placebo) as the most effective
- Pregnancy Outcome Measures: Birth Weight. [ Time Frame: at delivery ]Birth weight adjusted for gestational age at delivery is a measure of pregnancy outcome after treatment of HG.
- Newborn Outcome Measure: APGAR Score. [ Time Frame: at 1 minute and at 5 minutes after delivery ]
The APGAR score is the most common indicator of neonatal status immediately after delivery.
The test is done by a doctor, midwife, or nurse. The health care provider will examine the baby's:
Breathing effort Heart rate Muscle tone Reflexes Skin color Each category is scored with 0, 1, or 2, depending on the observed condition. The APGAR rating is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth.
- Systolic Blood Pressure [ Time Frame: 10 days ]Systolic BP was measured every day during the clonidine treatment (5 days) and placebo (5 days)
- Diastolic Blood Pressure [ Time Frame: 10 days ]Diastolic BP was recorded every day during clonidine (5 days) and placebo (5 days) cycle
Original Secondary Outcome:
- Number of doses of standard antiemetic drugs required in the two different periods. [ Time Frame: participants will be followed for the whole duration of hospital stay (10 days) comparing the first period of 5 days with the second of 5 days ]
- Number of days off-therapy, the TD system (clonidine /placebo) being applied only [ Time Frame: participants will be followed for the whole duration of hospital stay (10 days) comparing the first period of 5 days with the second of 5 days ]
- Number of Patients Choosing Active Treatment for Off-label, Compassionate Use. [ Time Frame: at 10 days since start of treatment ]the patients are asked to choose between two transdermal systems (active drug versus placebo)as the most effective
- Pregnancy Outcome Measures: Birth Weight. [ Time Frame: at delivery ]Birth weight adjusted for gestational age at delivery is a measure of pregnancy outcome after treatment of HG.
- Pregnancy outcome measure: APGAR score. [ Time Frame: 1 minute and 5 minutes after delivery ]APGAR score is the most common indicator of neonatal status immediately after delivery.
Information By: Azienda Ospedaliera Città della Salute e della Scienza di Torino
Dates:
Date Received: March 12, 2012
Date Started: February 2012
Date Completion:
Last Updated: March 31, 2014
Last Verified: March 2014
