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The cervix consists of connective tissue, smooth muscle, and parasympathetic innervation. Smooth muscle makes up about 15% of the cervix, is mainly found under the internal opening of the neck. Papaverine and its derivatives are musculotropic antispasmodic drugs that directly affect smooth muscle, the mechanism is to reduce the spasm of smooth muscle resulting in relaxation. Studies on the pharmacokinetics of this drug show that it has a half-life of 0.5-2 hours and its effect is apparent within 10 minutes.
Administration of antispasmodic drugs during childbirth is common in developing and developed countries. Based on previous studies, the use of these drugs during childbirth may lead to a faster opening of the cervix. Possible uses of Papaverine include, administered separately or in combination with other treatments such as rupture of amniotic membranes and/or Oxytocin administration. According to some studies, administration of Papaverine at birth can be used as a preventive or therapeutic strategy in cases of prolonged labor or first stage over 12 hours as defined in some studies. According to Kochran et al, who included 13 experiments with 1995 participants, the use of antispasmodic drugs shortened the first stage of labor by an average of 74.34 minutes. In 6 experiments that included 820 patients, the administration of antispasmodic drugs during labor increases the rate of cervical opening by an average of 0.61 cm per hour.
In addition to the muscle relaxation effect, studies have been published on the analgesic effect of PAPAVERINE for example in patients with urinary stones.
In the present study, the investigators want to test the effect of administering PAPAVERINE IV 80 mg within half an hour before the insertion of a catheter balloon for cervical ripening on the Bishop score after catheter removal between the two groups.
There are different methods of induction of labor, the choice of the best method for that patient depends on the bishop score, an estimate that is based on data related to the cervix such as opening, effacement and other parameters, also the choice of the method of induction depends on the obstetric history of the patient. A Bishop score less than 6 indicates an unriped cervix, therefore increasing the chance of labor induction failure,methods have been developed to ripen the cervix; among the methods are catheter balloon insertion and prostaglandins. The mechanisms by which the catheter works include a mechanical effect and indirect effect on local secretion of prostaglandins.
The cervix consists of connective tissue, smooth muscle, and parasympathetic innervation. Smooth muscle makes up about 15% of the cervix, is mainly found under the internal opening of the neck. Papaverine and its derivatives are musculotropic antispasmodic drugs that directly affect smooth muscle, the mechanism is to reduce the spasm of smooth muscle resulting in relaxation. Studies on the pharmacokinetics of this drug show that it has a half-life of 0.5-2 hours and its effect is apparent within 10 minutes.
Administration of antispasmodic drugs during childbirth is common in developing and developed countries. Based on previous studies, the use of these drugs during childbirth may lead to a faster opening of the cervix. Possible uses of Papaverine include, administered separately or in combination with other treatments such as rupture of amniotic membranes and/or Oxytocin administration. According to some studies, administration of Papaverine at birth can be used as a preventive or therapeutic strategy in cases of prolonged labor or first stage over 12 hours as defined in some studies. According to Kochran et al, who included 13 experiments with 1995 participants, the use of antispasmodic drugs shortened the first stage of labor by an average of 74.34 minutes. In 6 experiments that included 820 patients, the administration of antispasmodic drugs during labor increases the rate of cervical opening by an average of 0.61 cm per hour.
In addition to the muscle relaxation effect, studies have been published on the analgesic effect of PAPAVERINE for example in patients with urinary stones.
In the present study, the investigators want to test the effect of administering PAPAVERINE IV 80 mg within half an hour before the insertion of a catheter balloon for cervical ripening on the Bishop score after catheter removal between the two groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention group- IV PAPAVERINE 80 mg | Active Comparator | Administration of IV PAPAVERINE 80 mg in 100 ml of saline, once within half an hour before inserting a single-balloon balloon catheter |
|
| Conrol group- Placebo group. | Placebo Comparator | Administration of 100 ml of saline within half an hour before the insertion of a single-balloon catheter |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IV Papaverine 80 mg | Drug | Opium alkaloid antispasmodic drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| The delta Bishop score | The difference between the bishop score (a score of the cervix ripening) before and after the insertion of Foley catheter. Higher delta Bishop scores means better outcome | 1 year |
| Pain during insertion of the catheter | Pain during insertion of the catheter based on visual scale analoug (0-10) score, . The minimum is 0, the maximum is 10. Higher score means worse outcome | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Induction-delivery interval | Time from insertion of the catheter balloon to delivery. Longer interval means worse outcome | 2 years |
| Success | Bishop score (a score of cervix ripenining) after extraction of the catheter above or equal to 8. Bishop score above or equal to 8, means better outcome |
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Inclusion Criteria:
Exclusion Criteria:
Obstetrical research
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Raneen Abu Shqara, MD | Contact | +972549793591 | rabushqara@gmail.com | |
| Maya Frank Wolf, MD | Contact | +972507887800 | mayaw@gmc.gov.il |
| Name | Affiliation | Role |
|---|---|---|
| Maya Frank Wolf, MD | Galilee Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Galilee Medical Center | Recruiting | Nahariya | Northern District | Israel |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22895986 | Background | Rohwer AC, Khondowe O, Young T. Antispasmodics for labour. Cochrane Database Syst Rev. 2012 Aug 15;(8):CD009243. doi: 10.1002/14651858.CD009243.pub2. | |
| 14698825 | Background | Singh KC, Jain P, Goel N, Saxena A. Drotaverine hydrochloride for augmentation of labor. Int J Gynaecol Obstet. 2004 Jan;84(1):17-22. doi: 10.1016/s0020-7292(03)00276-5. |
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| ID | Term |
|---|---|
| D059787 | Acute Pain |
| D048949 | Labor Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D010208 | Papaverine |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D044182 | Benzylisoquinolines |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D053610 | Opiate Alkaloids |
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Double blinded randomized placebo controlled trial Group 1: will get IV PAPAVERINE 80 mg in 100 ml saline Group 2: will get IV 100 ml saline
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The participant will be blinded to the type of therapy they recieved. Inverstiagators will be blinded. Outcome assessor, including the physican that will assess the bishop score will be blinded Only the nurse that gives the therapy won't be blinded.
| Placebo | Drug | Placebo |
|
|
| 2 years |
| Use of other ripening method | The need for other ripening method due to low bishop score (<6) after extraction of the catheter balloon | 2 years |
| Insertion-extraction of the catheter interval | Time between insertion to extraction of the catheter balloon. | 2 years |
| Delivery method | Cesarean or vaginal delivery | 2 years |
| Maternal satisfaction | Based on visual scale analoug score for satisfaction (1-5), the minimum is 1, the maximum is 5, higher score means better outcome | 1 year |
| Apgar Score | The Apgar score, is a score given to the newborn in 1,5 and 10 minutes after birth, and is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. | 2 years |
| Cord pH | Cord blood gas analysis is an objective measure of the fetal metabolic condition at the time of delivery | 2 years |
| Need for neonatal intensive case admission | Is a measure of neonatal complications at birth | 2 years |
| 24299975 | Background | Ibrahim MI, Alzeeniny HA, Ellaithy MI, Salama AH, Abdellatif MA. Drotaverine to improve progression of labor among nulliparous women. Int J Gynaecol Obstet. 2014 Feb;124(2):112-7. doi: 10.1016/j.ijgo.2013.08.013. Epub 2013 Nov 7. |
| 19644697 | Background | Madhu C, Mahavarkar S, Bhave S. A randomised controlled study comparing Drotaverine hydrochloride and Valethamate bromide in the augmentation of labour. Arch Gynecol Obstet. 2010 Jul;282(1):11-5. doi: 10.1007/s00404-009-1188-8. Epub 2009 Jul 31. |
| 18289563 | Background | Snir N, Moskovitz B, Nativ O, Margel D, Sandovski U, Sulkes J, Livne PM, Lifshitz DA. Papaverine hydrochloride for the treatment of renal colic: an old drug revisited. A prospective, randomized study. J Urol. 2008 Apr;179(4):1411-4. doi: 10.1016/j.juro.2007.11.053. Epub 2008 Mar 4. |
| 38825005 | Derived | Abu Shqara R, Nakhleh Francis Y, Goldinfeld G, Haddad Y, Sgayer I, Lavinsky M, Lowenstein L, Frank Wolf M. Papaverine prior to catheter balloon insertion for labor induction: a randomized controlled trial. Am J Obstet Gynecol MFM. 2024 Jul;6(7):101388. doi: 10.1016/j.ajogmf.2024.101388. Epub 2024 May 31. |
| D007546 |
| Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |