Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum (CLONEMESI)

• PUQE score for assessment of severity in Hyperemesis Gravidarum [ Time Frame: change from baseline at 5 days and at 10 days ] [ Designated as safety issue: No ]

  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 ] [ Designated as safety issue: No ]

  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

  
  

• 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 ] [ Designated as safety issue: No ]
  
• 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 ] [ Designated as safety issue: No ]
  
• Number of patients choosing active treatment for off-label, compassionate use. [ Time Frame: at 10 days since start of treatment ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: Yes ]
  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 ] [ Designated as safety issue: Yes ]
  APGAR score is the most common indicator of neonatal status immediately after delivery.
  
  

• Morning urine ketonuria [ 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 ] [ Designated as safety issue: No ]
  Morning urine ketonuria is a simple direct marker of starving associated to nausea and vomiting
  
  

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 scores (operator mediated PUQE score and self administered VAS 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 .