Hexakaprone Treatment for Post-Partum Hemorrhage Prophylactic

Post-Partum Hemorrhage (PPH) is a common obstetrical complication. It may occur after both vaginal and cesarean delivery with a reported prevalence of 4-6% of deliveries [1]. Prophylactic treatment with oxytocin after fetus extraction is a common practice. [1,2]Transexamic acid - Hexakapron is a potent antifibrinolytic, it prevents lysine adhesion to plasminogen molecules by blocking its binding site. It can lower fibrinolysis rate and by that reduce bleeding [9]. Systematic treatment of anti-fibrinolytic drugs is in surgical practice after procedures such as coronary artery bypass graft, orthopedic surgeries and liver transplantation [10-13]. Hexakapron is an FDA approved drug, it is defined as a class B drug for pregnancy and lactation [12], it is already being used in a non-routine fashion in the delivery room during PPH.In obstetrics Hexakapron given before vaginal or cesarean delivery has been presumed to decrease blood loss and PPH. 2 studies that included 453 woman reported decrease in PPH (RR 0.51, 95% CI 0.36 to 0.72) [13-15]. However specific protocols for prophylactic treatment with Hexakapron as available with oxytocin are lacking, and further research is necessary to determine such guidelines [16].

Study Overview

• Status: Unknown
• Conditions: Post-Partum Hemorrhage
• Intervention / Treatment: Drug: Intervention group:

Detailed Description

Post-Partum Hemorrhage (PPH) is a common obstetrical complication. It may occur after both vaginal and cesarean delivery with a reported prevalence of 4-6% of deliveries [1]. Prophylactic treatment with oxytocin after fetus extraction is a common practice. [1,2] The increase in plasma volume during pregnancy, and uterine perfusion that reaches 750ml/min near term [3] are causes for excessive blood loss during vaginal or cesarean delivery. Blood loss is approximately 500ml and 1000ml during vaginal and cesarean delivery respectively. Studies have shown that blood transfusion treatment reaches to up to 6 % after cesarean section [5-6].

During placental delivery fibrinogen and fibrin degradation and plasminogen activation occurs. This causes fibrinolytic cascade that continues 6-10 hours post-partum [7]. Tissue injury during cesarean section may convert the hemostatic equilibrium towards fibrinolysis that results in excessive bleeding [8]/ Transexamic acid - Hexakapron is a potent antifibrinolytic, it prevents lysine adhesion to plasminogen molecules by blocking its binding site. It can lower fibrinolysis rate and by that reduce bleeding [9]. Systematic treatment of anti-fibrinolytic drugs is in surgical practice after procedures such as coronary artery bypass graft, orthopedic surgeries and liver transplantation [10-13]. Hexakapron is an FDA approved drug, it is defined as a class B drug for pregnancy and lactation [12], it is already being used in a non-routine fashion in the delivery room during PPH.

In obstetrics Hexakapron given before vaginal or cesarean delivery has been presumed to decrease blood loss and PPH. 2 studies that included 453 woman reported decrease in PPH (RR 0.51, 95% CI 0.36 to 0.72) [13-15]. However specific protocols for prophylactic treatment with Hexakapron as available with oxytocin are lacking, and further research is necessary to determine such guidelines [16].

PPH jeopardize young reproductive women's health, it is specifically related to major morbidity in the context of prior anemia which features this population in high rates [17]. PPH is the major maternal cause of death, with 100000 cases per year [6].

Thus the investigators sought to investigate the efficacy of Hexakapron, as a prophylactic treatment after vaginal delivery and cesarean section, in reducing PPH.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Normal vaginal delivery.
• Operative vaginal delivery (Vaccum and Forceps).
• Elective cesarean section.
• Age 18-50.

Exclusion Criteria:

• Excessive pain (VAS>4).
• Blood clotting disturbance or any major hematologic disease.
• Suspected Placenta-Previa.
• Multiple gestations.

• Contraindications for Hexakapron treatment:

  • Atrial fibrillation.
  • Coronary arteries stenting.
  • CABG(coronary artery bypass graft) in past year.
  • Hematuria (prior to pregnancy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group: Treatment with 1 gr hexakapron Intra-Venous (IV) after delivery of the fetus in addition to accepted treatment with oxytocin (10 units in 100ml NaCl (sodium chloride)0.9% solution IV). ( the oxytocin is the routine practice in our department).	Drug: Intervention group: Treatment with 1 gr hexakapron Intra-Venous (IV) after delivery of the fetus in addition to accepted treatment with oxytocin (10 units in 100ml NaCl 0.9% solution IV).; Other Names: Hexakaprone-Transexamic acid and oxytocin
No Intervention: Control: Treatment with oxytocin after fetal extraction (10 units in 100ml NaCl 0.9% solution IV). as commonly given for Post-Partum Hemorrhage (PPH) at our obstetrical ward.Active Comparator: (this is the routine practice in our department).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease post-partum hemoglobin decline.	Assessment of the hemoglobin decline - the decline will be calculated as the gap between the hemoglobin level prior delivery and the the hemoglobin measured 48-72 hours post delivery.	24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease PPH.	rates of Post-partum hemorrhage will be assessed by The difference between the groups	24 month
Decrease the need for post-partum uterine manual revision.	rates of Post-partum uterine manual revision will be assessed by The difference between the groups the difference will be assessed by a chi-square test.	24 month

Collaborators and Investigators

• Sponsor: Yariv yogev
• Collaborators: Rabin Medical Center
• Investigators: Principal Investigator: Yariv Yogev, professor, Director, Division of obstetrics and delivery

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: February 12, 2015
• First Posted (Estimate): February 13, 2015

Study Record Updates

• Last Update Posted (Estimate): September 9, 2015
• Last Update Submitted That Met QC Criteria: September 7, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 0656-14