Hyperemesis GravidarumPhase 3CLONEMESINCT01559012

Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum

A Phase 3 study testing Clonidine in people with Hyperemesis Gravidarum, run by A.O.U. Città della Salute e della Scienza at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Any age, women only
Conditions the study is for: Hyperemesis Gravidarum
What is being tested?: Clonidine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteItaly
Study dates: Feb 2012to Dec 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
Women only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

Language barrier.

Trial locations and contacts

1 site in 1 country.

Italy1 site

Ospedale Sant'Anna. Dipartimento di Ostetricia e Neonatologia. Servizio di Medicina Interna
Torino, 10126

Other trials in Italy

About this study

Official title: The CLONEMESI Study: a Randomized Placebo-controlled Study With Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum.

Read the 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 .

Conditions: Hyperemesis Gravidarum
Being tested: Clonidine
Keywords: Hyperemesis Gravidarum, treatment, transdermal clonidine
Medical subject headings: Hyperemesis Gravidarum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ClonidineDrug
Also called Catapresan TTS 2 transdermal patch
transdermal clonidine patch 5 mg q. 5 days

Study groups in NCT01559012
Study group	Role	What they receive
clonidine first - placebo second	Other	in this group patients are treated with transdermal clonidine first for 5 days then switch to placebo for 5 days Receives: Drug: Clonidine
placebo first - clonidine second	Other	in this group patients are treated with placebo first for 5 days then with transdermal clonidine for next 5 days Receives: Drug: Clonidine

What is being measured

The primary outcome is the main question the study is designed to answer.

PUQE Score for Assessment of Severity in Hyperemesis Gravidarum
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.
Measured: 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 Score for Assessment of Severity in Hyperemesis Gravidarum
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.
Measured: 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.

Secondary outcomes (8)

Morning Urine Ketonuria
Morning urine ketonuria is a simple direct marker of starving associated to nausea and vomiting
Measured: 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
Daily Doses of Standard Antiemetic Drugs Required in the Two Different Periods.
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.
Measured: 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
Number of Days Off i.v. Therapy, the TD System (Clonidine/Placebo) Being Applied Only
if the symptoms improve the patient and her doctors may decide to stop parenteral drugs continuing the TD system therapy.
Measured: 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
Number of Patients Choosing Active Treatment for Off-label, Compassionate Use.
the patients were asked to choose between two transdermal systems (active drug versus placebo) as the most effective
Measured: at 10 days since start of treatment
Pregnancy Outcome Measures: Birth Weight.
Birth weight adjusted for gestational age at delivery is a measure of pregnancy outcome after treatment of HG.
Measured: at delivery
Newborn Outcome Measure: APGAR Score.
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.
Measured: at 1 minute and at 5 minutes after delivery
Systolic Blood Pressure
Systolic BP was measured every day during the clonidine treatment (5 days) and placebo (5 days)
Measured: 10 days
Diastolic Blood Pressure
Diastolic BP was recorded every day during clonidine (5 days) and placebo (5 days) cycle
Measured: 10 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2012Dec 2012

First posted20 Mar 2012 (estimated)
Study startFeb 2012
Primary completionDec 2012
Study completionDec 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hyperemesis GravidarumStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01559012
Sponsor's protocol ID: Registro CE 409 det. 163/2012
Acronym: CLONEMESI
Status last verified: Mar 2014
First submitted: 12 Mar 2012
Last updated: 30 Apr 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Maina A, Arrotta M, Cicogna L, Donvito V, Mischinelli M, Todros T, Rivolo S. Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI. BJOG. 2014 Nov;121(12):1556-62. doi: 10.1111/1471-0528.12757. Epub 2014 Apr 1.
PubMed 24684734

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hyperemesis Gravidarum trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The CLONEMESI Study: a Randomized Placebo-controlled Study With Transdermal Clonidine in the Treatment of Severe Hyperemesis Gravidarum.
ClinicalTrials.gov ID: NCT01559012
Acronym / sponsor ID: CLONEMESI / Registro CE 409 det. 163/2012
Conditions: Hyperemesis Gravidarum
Keywords: Hyperemesis Gravidarum, treatment, transdermal clonidine
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: A.O.U. Città della Salute e della ScienzaUniversity, hospital or other
Study start: Feb 2012
Primary completion: Dec 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 20 Mar 2012 (estimated)
Results: Posted 30 Apr 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Setting. The trial is performed at a single hospital setting after admission of patients.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
clonidine first - placebo second	Other	Drug: Clonidinein this group patients are treated with transdermal clonidine first for 5 days then switch to placebo for 5 days
placebo first - clonidine second	Other	Drug: Clonidinein this group patients are treated with placebo first for 5 days then with transdermal clonidine for next 5 days

Who may qualify

Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (7 listed)

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,

Key exclusion criteria (1 listed)

Language barrier.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ClonidineAlso: Catapresan TTS 2 transdermal patchtransdermal clonidine patch 5 mg q. 5 days	Drug	clonidine first - placebo second, placebo first - clonidine second

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.

8 secondary outcomes

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
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
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
Number of Patients Choosing Active Treatment for Off-label, Compassionate Use.
Time frame: at 10 days since start of treatment
Pregnancy Outcome Measures: Birth Weight.
Time frame: at delivery
Newborn Outcome Measure: APGAR Score.
Time frame: at 1 minute and at 5 minutes after delivery
Systolic Blood Pressure
Time frame: 10 days
Diastolic Blood Pressure
Time frame: 10 days

Results and safety

Results posted to the registry on 30 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Clonidine First - Placebo Second	6	6
Placebo First - Clonidine Second	7	6

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.. Mean (95% Confidence Interval). Unit: units on a scale

Measure	Clonidine n = 12	Placebo n = 12
Value	6.3 (5.5-7.11)	8.5 (7.3-9.3)

Clonidine vs Placebo: Mean Difference (Final Values): 2.2 (95% CI 1.05 to 3.32), p = 0.001, Wilcoxon (Mann-Whitney)
Clonidine vs Placebo: within patient variation: 1.83 (95% CI 0.43 to 3.24), p <0.02, Wilcoxon (Mann-Whitney)

Population analysed: A sample size calculation for crossover studies using a model available on line (MGH Mallinckrodt General Clinical Research Center - Harvard Medical School) showed that a total of 12 patients were needed in order to detect a difference of 2 points of PUQE score between the two groups at P \< 0.01 and a beta \> 0.90.

Primary outcome: VAS Score for Assessment of Severity in Hyperemesis Gravidarum

Measure	Clonidine n = 12	Placebo n = 12
Value	22 (19 to 26)	29 (2.58)

Clonidine vs Placebo: Mean Difference (Final Values): 7 (95% CI 1.78 to 11.5), p = 0.009, Wilcoxon (Mann-Whitney)
Clonidine vs Placebo: within patient variation: 7.5 (95% CI 2.17 to 12.83), p <0.01, Wilcoxon (Mann-Whitney)

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 10 days of hospital stay. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Clonidine	0 of 6 (0%)	0 of 6 (0%)	Not reported
Placebo	0 of 7 (0%)	1 of 7 (14.3%)	Not reported

Limitations and caveats (from the sponsor): Efficacy and safety issues are represented by maternal exposure in a critical period for organogenesis and hypotensive effect of the drug. Findings based on a very limited number of women limit the reliability of results

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24684734Maina A, Arrotta M, Cicogna L, Donvito V, Mischinelli M, Todros T, Rivolo S. Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI. BJOG. 2014 Nov;121(12):1556-62. doi: 10.1111/1471-0528.12757. Epub 2014 Apr 1.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Aldo Maina, M.D. principal investigator

Dipartimento di Ostetricia e Neonatologia. Servizio di Medicina Interna. Ospedale Sant'Anna Torino

Tullia Todros, M.D. study chair

Head . Dipartimento di Ostetricia e Neonatologia. Università di Torino.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clonidine in people with Hyperemesis Gravidarum, run by A.O.U. Città della Salute e della Scienza at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01559012, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2014.