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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Aldo Maina, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
ClinicalTrials.gov Identifier:
NCT01559012
First received: March 12, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Hyperemesis Gravidarum
Drug: Clonidine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The CLONEMESI Study: a Randomized Placebo-controlled Study With Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum.

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera Città della Salute e della Scienza di Torino:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    Systolic BP was measured every day during the clonidine treatment (5 days) and placebo (5 days)

  • Diastolic Blood Pressure [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
    Diastolic BP was recorded every day during clonidine (5 days) and placebo (5 days) cycle


Enrollment: 13
Study Start Date: February 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
clonidine first - placebo second
in this group patients are treated with transdermal clonidine first for 5 days then switch to placebo for 5 days
Drug: Clonidine
transdermal clonidine patch 5 mg q. 5 days
Other Name: Catapresan TTS 2 transdermal patch
placebo first - clonidine second
in this group patients are treated with placebo first for 5 days then with transdermal clonidine for next 5 days
Drug: Clonidine
transdermal clonidine patch 5 mg q. 5 days
Other Name: Catapresan TTS 2 transdermal patch

Detailed Description:

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 .

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Gestational age 6-12 weeks and a major grade of HG clinical severity defined as follows:
  • a PUQE score index ≥ 13 associated to one or more of the following conditions:
  • weight loss > 5% of pregravidic weight,
  • electrolyte disturbances,
  • dehydration,
  • duration of symptoms > 10 days ,
  • inadequate food and drink intake

Exclusion Criteria:

  • Language barrier.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559012

Locations
Italy
Ospedale Sant'Anna. Dipartimento di Ostetricia e Neonatologia. Servizio di Medicina Interna
Torino, Italy, 10126
Sponsors and Collaborators
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Investigators
Principal Investigator: Aldo Maina, M.D. Dipartimento di Ostetricia e Neonatologia. Servizio di Medicina Interna. Ospedale Sant'Anna Torino
Study Chair: Tullia Todros, M.D. Head . Dipartimento di Ostetricia e Neonatologia. Università di Torino.
  More Information

No publications provided

Responsible Party: Aldo Maina, M.D. Unit of Obstetric Medicine. Principal Investigator, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
ClinicalTrials.gov Identifier: NCT01559012     History of Changes
Other Study ID Numbers: Registro CE 409 det. 163/2012
Study First Received: March 12, 2012
Results First Received: February 12, 2014
Last Updated: March 31, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliera Città della Salute e della Scienza di Torino:
Hyperemesis Gravidarum
treatment
transdermal clonidine

Additional relevant MeSH terms:
Hyperemesis Gravidarum
Morning Sickness
Pregnancy Complications
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Clonidine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 29, 2014