<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03025581</url>
  </required_header>
  <id_info>
    <org_study_id>0091-HYMC</org_study_id>
    <nct_id>NCT03025581</nct_id>
  </id_info>
  <brief_title>Does Nipple Stimulation Shorten Time to Vaginal Birth in Women With Term PROM?</brief_title>
  <acronym>NIPROM</acronym>
  <official_title>Does Nipple Stimulation Shorten Time to Vaginal Birth in Women With Term PROM? (NIPROM Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hillel Yaffe Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hillel Yaffe Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Premature Rupture of Membranes (PROM) is defined as the rupture of membranes before the onset&#xD;
      of regular uterine contractions.&#xD;
&#xD;
      PROM occurs in approximately 10% of all pregnancies (ranging from 2.7% to 17%), with 60% to&#xD;
      80% of cases occurring at term. Approximately 90% of patients' experience PROM enter&#xD;
      spontaneous labor within 24 hours, but disagreement exists among health care providers on the&#xD;
      optimal management of women with PROM, particularly the need for and timing of inductions.&#xD;
&#xD;
      Nipple stimulation is a non-medical natural method for induction of labor. Previous studies&#xD;
      demonstrated its effectiveness for initiating labor within 72 hours in women with favorable&#xD;
      cervices. The actual mechanism by which such a technique results in cervical ripening is not&#xD;
      well understood.&#xD;
&#xD;
      In this study, we aim to assess the effectiveness of nipple stimulation in gravid women with&#xD;
      term PROM choosing expectant management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The participants in the study will be randomized into two groups of expectant management&#xD;
      (patients desire an active approach will be excluded).&#xD;
&#xD;
      All eligible participants will be randomly allocated to either intervention or control group.&#xD;
      They will be followed from the time of presentation with rupture of membranes at the ER and&#xD;
      until the time of delivery. Prophylactic antibiotics will be administered after 18 hours from&#xD;
      rupture of membranes as per departmental policy.&#xD;
&#xD;
      On admission, and after validating inclusion criteria, women will be offered to join the&#xD;
      study. For the intervention group women will be instructed to gently massage alternate&#xD;
      breasts, especially around the nipples for 15 minutes every 6 hours until the appearance of&#xD;
      regular contractions but not more than 24 hours. Moist cloth or lubricating or moisturizing&#xD;
      cream will be offered to facilitate the procedure according to individual preferences. In the&#xD;
      control group all participants will be asked to avoid any breast stimulation during the study&#xD;
      period.&#xD;
&#xD;
      For both groups maternal surveillance will include obstetrician assessment every 6 hours or&#xD;
      per maternal request if painful contractions. Every assessment will include documenting&#xD;
      maternal vital signs, sense of contraction, fetal cardiotocographic assessment and vaginal&#xD;
      examination if painful contractions. After delivery,all participants will be requested to&#xD;
      fill a satisfaction questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">January 2018</completion_date>
  <primary_completion_date type="Anticipated">January 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment</measure>
    <time_frame>One year</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Premature Rupture of Fetal Membranes</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nipple stimulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention (expectant management only).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Nipple stimulation</intervention_name>
    <description>For the intervention group participants will be instructed to gently massage alternate breasts, especially around the nipples for 15 minutes every 6 hours until the appearance of regular contractions but not more than 24 hours. Moist cloth or lubricating or moisturizing cream will be offered to facilitate the procedure according to individual preferences. In the control group all participants will be asked to avoid any breast stimulation during the study period.</description>
    <arm_group_label>Intervention group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primagravidas at term (&gt;37) weeks having PROM&#xD;
&#xD;
          -  Singleton pregnancies&#xD;
&#xD;
          -  Cephalic presentation&#xD;
&#xD;
          -  Unfavorable cervix (Bishop score &lt;7)&#xD;
&#xD;
          -  Desire an expectant management&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior cesarean section/ uterine rupture / transmural uterine incision&#xD;
&#xD;
          -  Non reassuring fetal heart rate monitoring (Category III)&#xD;
&#xD;
          -  Signs of fetal or maternal infection&#xD;
&#xD;
          -  Time elapsed since PROM &gt; 6 hours&#xD;
&#xD;
          -  Meconium or blood-stained amniotic fluid&#xD;
&#xD;
          -  Any contraindication for vaginal birth&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mordechai Hallak, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Obstetrics &amp; Gynecology, Hillel Yaffe Medical Center, Hadera</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rinat Gabbay, M.D</last_name>
    <role>Study Director</role>
    <affiliation>Department of Obstetrics &amp; Gynecology, Hillel Yaffe Medical Center, Hadera</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ofer Limonad, M.D</last_name>
    <email>oferlimonad@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Esti Maor, M.D</last_name>
    <email>estigal02@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hillel Yaffe Medical Center</name>
      <address>
        <city>Hadera</city>
        <country>Israel</country>
      </address>
    </facility>
    <contact>
      <last_name>Ofer Limonad, M.D</last_name>
      <email>oferlimonad@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Esti Maor, M.D</last_name>
      <email>oferlimonad@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <results_reference>
    <citation>Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL, Wang EE, Weston JA, Willan AR. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. N Engl J Med. 1996 Apr 18;334(16):1005-10. doi: 10.1056/NEJM199604183341601.</citation>
    <PMID>8598837</PMID>
  </results_reference>
  <results_reference>
    <citation>Cahill AG, Tuuli MG. Labor in 2013: the new frontier. Am J Obstet Gynecol. 2013 Dec;209(6):531-4. doi: 10.1016/j.ajog.2013.04.016. Epub 2013 Apr 10.</citation>
    <PMID>23583208</PMID>
  </results_reference>
  <results_reference>
    <citation>Christensson K, Nilsson BA, Stock S, Matthiesen AS, Uvnas-Moberg K. Effect of nipple stimulation on uterine activity and on plasma levels of oxytocin in full term, healthy, pregnant women. Acta Obstet Gynecol Scand. 1989;68(3):205-10. doi: 10.3109/00016348909020990.</citation>
    <PMID>2618602</PMID>
  </results_reference>
  <results_reference>
    <citation>Elliott JP, Flaherty JF. The use of breast stimulation to ripen the cervix in term pregnancies. Am J Obstet Gynecol. 1983 Mar 1;145(5):553-6. doi: 10.1016/0002-9378(83)91194-8.</citation>
    <PMID>6338721</PMID>
  </results_reference>
  <results_reference>
    <citation>Elliott JP, Flaherty JF. The use of breast stimulation to prevent postdate pregnancy. Am J Obstet Gynecol. 1984 Jul 15;149(6):628-32. doi: 10.1016/0002-9378(84)90247-3.</citation>
    <PMID>6377899</PMID>
  </results_reference>
  <results_reference>
    <citation>Hill WC, Moenning RK, Katz M, Kitzmiller JL. Characteristics of uterine activity during the breast stimulation stress test. Obstet Gynecol. 1984 Oct;64(4):489-92.</citation>
    <PMID>6483296</PMID>
  </results_reference>
  <results_reference>
    <citation>Johnson JW, Daikoku NH, Niebyl JR, Johnson TR Jr, Khouzami VA, Witter FR. Premature rupture of the membranes and prolonged latency. Obstet Gynecol. 1981 May;57(5):547-56.</citation>
    <PMID>7219903</PMID>
  </results_reference>
  <results_reference>
    <citation>Kavanagh J, Kelly AJ, Thomas J. Breast stimulation for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2005 Jul 20;2005(3):CD003392. doi: 10.1002/14651858.CD003392.pub2.</citation>
    <PMID>16034897</PMID>
  </results_reference>
  <results_reference>
    <citation>Leake RD, Buster JE, Fisher DA. The oxytocin secretory response to breast stimulation in women during the menstrual cycle. Am J Obstet Gynecol. 1984 Feb 15;148(4):457-60. doi: 10.1016/0002-9378(84)90726-9.</citation>
    <PMID>6696003</PMID>
  </results_reference>
  <results_reference>
    <citation>Mishanina E, Rogozinska E, Thatthi T, Uddin-Khan R, Khan KS, Meads C. Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis. CMAJ. 2014 Jun 10;186(9):665-73. doi: 10.1503/cmaj.130925. Epub 2014 Apr 28.</citation>
    <PMID>24778358</PMID>
  </results_reference>
  <results_reference>
    <citation>Salmon YM, Kee WH, Tan SL, Jen SW. Cervical ripening by breast stimulation. Obstet Gynecol. 1986 Jan;67(1):21-4.</citation>
    <PMID>3940333</PMID>
  </results_reference>
  <results_reference>
    <citation>Viegas OA, Arulkumaran S, Gibb DM, Ratnam SS. Nipple stimulation in late pregnancy causing uterine hyperstimulation and profound fetal bradycardia. Br J Obstet Gynaecol. 1984 Apr;91(4):364-6. doi: 10.1111/j.1471-0528.1984.tb05924.x.</citation>
    <PMID>6712896</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>January 16, 2017</last_update_submitted>
  <last_update_submitted_qc>January 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fetal Membranes, Premature Rupture</mesh_term>
    <mesh_term>Rupture</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03025581
org study id: 0091-HYMC
nct id: NCT03025581
lead sponsor: 
has dmc: No
Premature Rupture of Membranes (PROM) is defined as the rupture of membranes before the onset
      of regular uterine contractions.

      PROM occurs in approximately 10% of all pregnancies (ranging from 2.7% to 17%), with 60% to
      80% of cases occurring at term. Approximately 90% of patients' experience PROM enter
      spontaneous labor within 24 hours, but disagreement exists among health care providers on the
      optimal management of women with PROM, particularly the need for and timing of inductions.

      Nipple stimulation is a non-medical natural method for induction of labor. Previous studies
      demonstrated its effectiveness for initiating labor within 72 hours in women with favorable
      cervices. The actual mechanism by which such a technique results in cervical ripening is not
      well understood.

      In this study, we aim to assess the effectiveness of nipple stimulation in gravid women with
      term PROM choosing expectant management.
The participants in the study will be randomized into two groups of expectant management
      (patients desire an active approach will be excluded).

      All eligible participants will be randomly allocated to either intervention or control group.
      They will be followed from the time of presentation with rupture of membranes at the ER and
      until the time of delivery. Prophylactic antibiotics will be administered after 18 hours from
      rupture of membranes as per departmental policy.

      On admission, and after validating inclusion criteria, women will be offered to join the
      study. For the intervention group women will be instructed to gently massage alternate
      breasts, especially around the nipples for 15 minutes every 6 hours until the appearance of
      regular contractions but not more than 24 hours. Moist cloth or lubricating or moisturizing
      cream will be offered to facilitate the procedure according to individual preferences. In the
      control group all participants will be asked to avoid any breast stimulation during the study
      period.

      For both groups maternal surveillance will include obstetrician assessment every 6 hours or
      per maternal request if painful contractions. Every assessment will include documenting
      maternal vital signs, sense of contraction, fetal cardiotocographic assessment and vaginal
      examination if painful contractions. After delivery,all participants will be requested to
      fill a satisfaction questionnaire.
allocation: Randomized
intervention model: Parallel Assignment
masking: None (Open Label)
measure: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
time frame: One year
arm group label: Intervention group
arm group type: Active Comparator
description: Nipple stimulation.
arm group label: Control group
arm group type: No Intervention
description: No intervention (expectant management only).
intervention type: Other
intervention name: Nipple stimulation
description: For the intervention group participants will be instructed to gently massage alternate breasts, especially around the nipples for 15 minutes every 6 hours until the appearance of regular contractions but not more than 24 hours. Moist cloth or lubricating or moisturizing cream will be offered to facilitate the procedure according to individual preferences. In the control group all participants will be asked to avoid any breast stimulation during the study period.
arm group label: Intervention group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mordechai Hallak, M.D
role: Principal Investigator
affiliation: Department of Obstetrics & Gynecology, Hillel Yaffe Medical Center, Hadera
last name: Rinat Gabbay, M.D
role: Study Director
affiliation: Department of Obstetrics & Gynecology, Hillel Yaffe Medical Center, Hadera
last name: Ofer Limonad, M.D
email: oferlimonad@gmail.com
last name: Esti Maor, M.D
email: estigal02@yahoo.com
facility: 
contact: 
contact backup: 
country: Israel
citation: Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL, Wang EE, Weston JA, Willan AR. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. N Engl J Med. 1996 Apr 18;334(16):1005-10. doi: 10.1056/NEJM199604183341601.
PMID: 8598837
citation: Cahill AG, Tuuli MG. Labor in 2013: the new frontier. Am J Obstet Gynecol. 2013 Dec;209(6):531-4. doi: 10.1016/j.ajog.2013.04.016. Epub 2013 Apr 10.
PMID: 23583208
citation: Christensson K, Nilsson BA, Stock S, Matthiesen AS, Uvnas-Moberg K. Effect of nipple stimulation on uterine activity and on plasma levels of oxytocin in full term, healthy, pregnant women. Acta Obstet Gynecol Scand. 1989;68(3):205-10. doi: 10.3109/00016348909020990.
PMID: 2618602
citation: Elliott JP, Flaherty JF. The use of breast stimulation to ripen the cervix in term pregnancies. Am J Obstet Gynecol. 1983 Mar 1;145(5):553-6. doi: 10.1016/0002-9378(83)91194-8.
PMID: 6338721
citation: Elliott JP, Flaherty JF. The use of breast stimulation to prevent postdate pregnancy. Am J Obstet Gynecol. 1984 Jul 15;149(6):628-32. doi: 10.1016/0002-9378(84)90247-3.
PMID: 6377899
citation: Hill WC, Moenning RK, Katz M, Kitzmiller JL. Characteristics of uterine activity during the breast stimulation stress test. Obstet Gynecol. 1984 Oct;64(4):489-92.
PMID: 6483296
citation: Johnson JW, Daikoku NH, Niebyl JR, Johnson TR Jr, Khouzami VA, Witter FR. Premature rupture of the membranes and prolonged latency. Obstet Gynecol. 1981 May;57(5):547-56.
PMID: 7219903
citation: Kavanagh J, Kelly AJ, Thomas J. Breast stimulation for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2005 Jul 20;2005(3):CD003392. doi: 10.1002/14651858.CD003392.pub2.
PMID: 16034897
citation: Leake RD, Buster JE, Fisher DA. The oxytocin secretory response to breast stimulation in women during the menstrual cycle. Am J Obstet Gynecol. 1984 Feb 15;148(4):457-60. doi: 10.1016/0002-9378(84)90726-9.
PMID: 6696003
citation: Mishanina E, Rogozinska E, Thatthi T, Uddin-Khan R, Khan KS, Meads C. Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis. CMAJ. 2014 Jun 10;186(9):665-73. doi: 10.1503/cmaj.130925. Epub 2014 Apr 28.
PMID: 24778358
citation: Salmon YM, Kee WH, Tan SL, Jen SW. Cervical ripening by breast stimulation. Obstet Gynecol. 1986 Jan;67(1):21-4.
PMID: 3940333
citation: Viegas OA, Arulkumaran S, Gibb DM, Ratnam SS. Nipple stimulation in late pregnancy causing uterine hyperstimulation and profound fetal bradycardia. Br J Obstet Gynaecol. 1984 Apr;91(4):364-6. doi: 10.1111/j.1471-0528.1984.tb05924.x.
PMID: 6712896
responsible party type: Sponsor
mesh term: Fetal Membranes, Premature Rupture
mesh term: Rupture
sharing ipd: No