Prospective, Single Arm Pivotal Clinical Trial Designed to Assess the Safety and Effectiveness of the Jada System in Treating Primary Postpartum Hemorrhage
Phase: NA
Conditions: Postpartum Hemorrhage
Sponsor: Alydia Health

           
PEARLE Study 
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CIP-01 v2.6 
 
CLINICAL INVESTIGATION PLAN (PROTOCOL) 
PEARLE: Prospective, Single Arm, Pivotal Clinical Trial Designed to Assess 
the Safety and Effectiveness of the Jada™ System In Treating 
Primary Postpartum Hemorrhage 
 
Short title: 
PEARLE Study 
Test device: 
Jada System 
Clinical study phase: 
Pivotal 
Version Date: 
25FEB2019 
Study no.: 
PPH-02 
Version No.: 
CIP-01 v2.6 
Sponsor: 
Alydia Health 
3475 Edison Way, Suite J 
Menlo Park, California 94025 USA 
Study Principal Investigator: Mary D’Alton, MD 
Columbia University 
 
Sponsor Contact:  
Kathryn Wine, MPH 
Vice President of Clinical Operations 
kathryn@alydiahealth.com 
415.990.4104 
Independent Medical 
Monitor: 
Christopher Grover, MD 
Clinical Professor of Medicine, UC Davis 
cgrover@sbcglobal.net 
650.960.5159 
 
Confidential 
The information provided in this document is strictly confidential and is intended solely for the guidance 
of the clinical investigation.  Reproduction or disclosure of this document - whether in part or in full - to 
parties not associated with the clinical investigation, or its use for any other purpose, without the prior 
written consent of the sponsor is not permitted. The information contained in the document is the sole 
property of Alydia Health. 
Throughout this document, symbols indicating proprietary names (, TM) may not be displayed.  Hence, 
the appearance of product names without these symbols does not imply that these names are not protected. 
This study shall be conducted under Institutional Review Board approval and in compliance with United 
States (U.S.) Food and Drug Administration (FDA) regulations, ISO 14155 (2011), the ethical principles 
that have their origin in the Declaration of Helsinki and all applicable privacy requirements. 
 

           
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Investigator Certification 
 
Prior to participation in the PEARLE Study as an Investigator, I understand that I must obtain written 
approval from my Institutional Review Board (IRB). 
 
As an Investigator, I must also: 
1. Conduct the study in accordance with the study protocol, United States (U.S.) Food and Drug 
Administration (FDA) regulations (21 Code of Federal Regulations (CFR) Parts 812, 50, 54, & 56), 
ISO 14155, the ethical principles that have their origin in the Declaration of Helsinki and all 
applicable privacy requirements. 
2. Complete required study training prior to study participation. 
3. Ensure that the study is not commenced until IRB approval has been obtained. 
4. Ensure that written informed consent is obtained from each subject prior to enrollment into the 
study, using the most recently IRB-approved subject Informed Consent Form. 
5. Provide all required data and reports and agree to allow source document verification of study data 
with subject’s medical records. 
6. Allow Sponsor personnel and its designees, as well as U.S. FDA representatives and representatives 
from other public health agencies, to inspect and copy any documents pertaining to this clinical 
investigation. 
 
Investigator Signature  
I have read and understand the contents of the PEARLE Study protocol (CIP-01 v2.6) and agree to abide 
by the requirements set forth in this document.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed name 
 
 
 
 
 
Institution 
 
 
 
 

           
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Revision History 
Version Number 
Description of Change 
Effective Date 
Version 1 
Initial release. Note: Initial protocol 
numbered CIV-PIVOTAL-1.0. Version 
030716/S2. 
7 April 2016 
Version 1.1 
Change to informed consent section to 
allow informed consent to be obtained 
after the onset of labor.  Note: Protocol 
revision numbered CIV-PIVOTAL-1.1.   
20 December 2016 
Version 2 
Protocol rewrite to change the primary 
endpoint and statistical analysis plan.  
Editorial and administrative changes also 
made. Note: Protocol revision 
numbering changed to PPH-02 version 
2.   
24 February 2017 
Version 2.1 
Minor edits to protocol to clarify 
primary effectiveness endpoint, add a 
secondary endpoint for maternal 
morbidity, clarify the definition of time 
to hemorrhage cessation, and clarify the 
statistics section.  Edits made in 
response to FDA Study Design 
Considerations identified in February 24, 
2017 approval letter for S006. 
11 April 2017 
Version 2.2 
Minor edits to protocol to clarify 
statistical analysis in section 5.3.1.  Edits 
made in response to FDA Study Design 
Considerations identified in the IDE 
Approval Letter dated April 11, 2017 for 
S007. 
7 July 2017 
Version 2.3 
Minor edits to protocol to clarify 
statistical analysis and sample size in 
Section 5.3. Edits made in response to 
FDA Study Design Considerations 
identified in the IDE Approval Letter 
dated July 7, 2017 for S008.  Additional 
minor edits made to cover sheet and 
Section 9 for study consistency. 
6 November 2017 
Version 2.4 
Minor edits to protocol to clarify 
statistical analysis and sample size in 
Section 5.3. Edits made in response to 
FDA Study Design Considerations 
identified in the IDE Approval Letter 
dated November 6, 2017 for S010.   
19 December 2017 
Version 2.5 
Edits to clarify inclusion and exclusion 
criteria and the schedule of assessments.  
Added the consent bracelet as an 
identifier for consented subjects.  
Eliminated OUS sites and increased 
number of sites to 12. Edits to the risk 
17 July 2018 

           
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CIP-01 v2.6 
 
 
 
 
and potential benefits sections and to the 
name of the Device. Updated the contact 
information and other minor corrections. 
A section on training was included. The 
secondary endpoint of time to PPH 
control was refined and the steps of 
Device use were clarified.  
Version 2.6 
Updated name of Sponsor to Alydia 
Health and name of product to Jada 
System. Updated picture of consent 
bracelet. Updated maximum number of 
sites to 20 in the U.S. or O.U.S. Revised 
secondary endpoints. Revised one 
inclusion and one exclusion criterion. 
Revised poolability section. Added study 
poster as optional recruitment tool. 
25FEB2019 

           
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List of abbreviations 
Abbreviation  Definition 
ADE 
 
Adverse device effect 
AE 
 
Adverse event 
AMTSL 
 
Active Management of the Third Stage of Labor 
CBC 
 
Complete blood count 
CRF 
 
Case report form 
FDA 
 
Food and Drug Administration 
FIH 
 
First-in-Human 
GCP 
 
Good clinical practices 
GMP 
 
Good manufacturing practices 
ICF 
 
Informed consent form 
ICU 
 
Intensive care unit 
IDE 
 
Investigational device exception 
IFU 
 
Instructions for use 
IRB 
 
Institutional review board 
ISO 
 
International Standards Organization 
IV 
 
Intravenous 
ITT 
 
Intent to Treat 
O.U.S. 
 
Outside the United States 
PPH 
 
Postpartum hemorrhage 
SADE 
 
Serious adverse device event 
SAE 
 
Serious adverse event 
SAS 
 
Statistical Analysis System 
UADE 
 
Unanticipated adverse device effect 
U.S. 
 
United States 
WHO 
 
World Health Organization 
 
 
 

           
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Table of Contents 
1.0 
Study Summary ............................................................................................................................................... 8 
2.0 
Postpartum Hemorrhage Background .......................................................................................................... 9 
 
Definition and Prevalence of Postpartum Hemorrhage ................................................................................................... 9 
 
Causes of Postpartum Hemorrhage ............................................................................................................................. 10 
 
Currently Available Treatment and Prevention Strategies ............................................................................................. 10 
3.0 
Device Description ........................................................................................................................................ 11 
 
Intended Use ................................................................................................................................................................ 11 
 
Jada System Description .............................................................................................................................................. 11 
 
Jada Overview ............................................................................................................................................................. 12 
3.3.1 
Mechanism of Action ............................................................................................................................................... 13 
 
Prior Bench and Animal Testing ................................................................................................................................... 14 
3.4.1 
Benchtop Studies .................................................................................................................................................... 14 
3.4.2 
Safety Studies ......................................................................................................................................................... 14 
3.4.3 
Animal Studies ........................................................................................................................................................ 15 
 
First in Human Study Feasibility Study ......................................................................................................................... 15 
 
Risk Analysis ................................................................................................................................................................ 15 
3.6.1 
Potential Risks to Study Subjects ............................................................................................................................ 15 
3.6.2 
Risk Detection and Mitigation .................................................................................................................................. 16 
 
Potential Benefits of the Intervention ............................................................................................................................ 16 
4.0 
Study Objectives ........................................................................................................................................... 17 
 
Purpose of the Study .................................................................................................................................................... 17 
 
Study Endpoints ........................................................................................................................................................... 17 
4.2.1 
Primary Effectiveness Endpoint ............................................................................................................................... 17 
4.2.2 
Primary Safety Endpoint .......................................................................................................................................... 17 
4.2.3 
Secondary Endpoints .............................................................................................................................................. 17 
 
Overall Study Success ................................................................................................................................................. 17 
5.0 
Study Design ................................................................................................................................................. 18 
 
Overview ...................................................................................................................................................................... 18 
 
Site Selection ............................................................................................................................................................... 18 
 
Study Training .............................................................................................................................................................. 18 
 
Study Population .......................................................................................................................................................... 19 
5.4.1 
Number of Subjects and Sample Size Calculation ................................................................................................... 19 
5.4.2 
Source of Subjects .................................................................................................................................................. 20 
5.4.3 
Inclusion/Exclusion Criteria ...................................................................................................................................... 20 
5.4.4 
Subject Withdrawal and Termination ....................................................................................................................... 21 
 
Duration of Study and Subject Participation .................................................................................................................. 21 
 
Justification for Study ................................................................................................................................................... 21 
6.0 
Study Procedures ......................................................................................................................................... 22 
 
Subject Recruitment ..................................................................................................................................................... 22 
 
Subject Consent ........................................................................................................................................................... 22 
 
Subject Pre-Enrollment Screening ................................................................................................................................ 24 
 
Subject Enrollment ....................................................................................................................................................... 24 
 
Intervention .................................................................................................................................................................. 24 
 
Post-procedure Follow-up ............................................................................................................................................ 25 

           
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Six-week Follow-up ...................................................................................................................................................... 25 
 
Summary Table of Clinical Assessments ...................................................................................................................... 25 
7.0 
Safety and Adverse Events .......................................................................................................................... 26 
 
Definitions .................................................................................................................................................................... 26 
7.1.1 
Adverse event ......................................................................................................................................................... 26 
7.1.2 
Adverse device effect .............................................................................................................................................. 26 
7.1.3 
Device deficiency..................................................................................................................................................... 26 
7.1.4 
Device failure ........................................................................................................................................................... 26 
7.1.5 
Device malfunction .................................................................................................................................................. 26 
7.1.6 
Device misuse ......................................................................................................................................................... 26 
7.1.7 
Device-related adverse event .................................................................................................................................. 27 
7.1.8 
Near incident ........................................................................................................................................................... 27 
7.1.9 
Serious adverse device effect .................................................................................................................................. 27 
7.1.10 
Serious adverse event (SAE) .............................................................................................................................. 27 
7.1.11 
Unanticipated adverse device effect ................................................................................................................... 27 
 
Classifications for Adverse Event Assessment ............................................................................................................. 27 
7.2.1 
Seriousness............................................................................................................................................................. 27 
7.2.2 
Severity ................................................................................................................................................................... 28 
7.2.3 
Causal relationship .................................................................................................................................................. 28 
7.2.4 
Anticipated .............................................................................................................................................................. 28 
 
Assessments and documentation of adverse events .................................................................................................... 28 
 
Reporting of serious adverse events and near incidents ............................................................................................... 29 
 
Device Deficiencies ...................................................................................................................................................... 29 
 
Study Termination ........................................................................................................................................................ 29 
8.0 
Data Collection, Reporting and Quality Assurance ................................................................................... 29 
 
Case Report Forms ...................................................................................................................................................... 29 
 
Protocol Deviations ...................................................................................................................................................... 29 
 
Efforts to Minimize Data Loss ....................................................................................................................................... 30 
 
Data Confidentiality ...................................................................................................................................................... 30 
 
Quality Assurance of the Data ...................................................................................................................................... 30 
 
Monitoring Procedures ................................................................................................................................................. 30 
 
Publication Policy ......................................................................................................................................................... 31 
9.0 
Statistical Analysis Plan ............................................................................................................................... 31 
 
Introduction .................................................................................................................................................................. 31 
 
Study Endpoint Analysis ............................................................................................................................................... 31 
 
Primary Effectiveness Endpoint – Treatment Success .................................................................................................. 31 
 
Study Success ............................................................................................................................................................. 32 
 
Secondary Endpoints ................................................................................................................................................... 32 
 
Analysis Cohorts .......................................................................................................................................................... 32 
 
Derived Data – Change-from-Baseline Parameters ...................................................................................................... 33 
 
Statistical Methods ....................................................................................................................................................... 33 
 
Subgroup Analysis ....................................................................................................................................................... 33 
 
Poolability ..................................................................................................................................................................... 33 
 
Lost to Follow-up .......................................................................................................................................................... 34 
 
Dropout Mechanism and Analysis ................................................................................................................................ 34 
10.0 
References ..................................................................................................................................................... 34 

           
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1.0 
Study Summary 
Title: 
Prospective, Single Arm, Pivotal Clinical Trial Designed to Assess the Safety 
and Effectiveness of the Jada System In Treating Primary Postpartum 
Hemorrhage (“PPH”)  
Short Title: 
PEARLE Study 
Design: 
Prospective, single-arm, literature-controlled, multi-center study  
Purpose: 
Evaluate the safety and effectiveness of the Jada System in the control and 
reduction of primary postpartum hemorrhage. 
Inclusion 
Criteria: 
1. Adult Female, 18 years of age or older at time of consent. 
2. Able to understand and provide informed consent to participate in the 
study. 
3. Diagnosis of PPH with suspected atony within 24 hours after vaginal 
or c-section delivery. 
4. EBL, to be determined when investigator is ready to have the Jada peel 
pack opened: 
Vaginal delivery: 500 – 1500 ml EBL or 
C-section delivery: 1000 – 1500 ml EBL 
5. Failed first-line intervention of uterotonics and uterine 
massage/bimanual uterine massage to stop bleeding. 
Note:  Uterotonic administration may continue concomitant with and 
post Jada use, as long as such use does not exceed the maximum dose 
of the drug. 
Exclusion 
Criteria: 
1. EBL >1500ml, to be determined when investigator is ready to have the 
Jada peel pack opened. 
2. Delivery at a gestational age < 34 weeks. 
3. For C-sections: Cervix < 3 cm dilated before use of Jada.  
4. PPH that the investigator determines to require more aggressive 
treatment, including any of the following: 
a) hysterectomy; 
b) b-lynch suture; 
c) uterine artery embolization or ligation; 
d) hypogastric ligation. 
5. Known uterine anomaly. 
6. Ongoing intrauterine pregnancy. 
7. Placenta abnormality including any of the following: 
a) known placenta accreta; 
b) retained placenta with known risk factors for placenta accreta (e.g. 
history of prior uterine surgery, including prior c-section and placenta 
previa); 
c) retained placenta without easy manual removal. 
8. Known uterine rupture.  
9. Unresolved uterine inversion. 
10. Subject has undergone intrauterine balloon therapy or uterine packing 
for tamponade treatment of this PPH prior to use of the Jada System. 
11. Current cervical cancer. 
12. Current purulent infection of vagina, cervix, uterus. 
13. Diagnosis of coagulopathy.  

           
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Duration of 
Study: 
It is expected to take approximately 12-18 months to enroll, treat, and follow-
up all 107 subjects. 
Primary  
Safety 
Endpoint: 
Incidence, severity and seriousness of device-related Adverse Events (AEs).  
Primary 
Effectiveness 
Endpoint: 
Control of postpartum hemorrhage, defined as the avoidance of non-surgical, 
second-line or surgical intervention to control uterine hemorrhage after the use 
of the Jada System per the Instructions for Use. 
 
Non-surgical, second line procedures include uterine balloon therapy, uterine 
packing, or uterine artery embolization.  Surgical intervention includes 
procedures such as uterine arterial ligation, uterine compression sutures or 
hysterectomy. 
 
Note: Continuation of the administration of uterotonics concomitant with and 
post Jada System use is standard of care and does not constitute failure of the 
primary effectiveness endpoint.  
Statistical 
Analysis Plan 
Summary: 
The primary effectiveness objective of this Pivotal Study is to show that the 
observed Treatment Success Rate is not worse than the rate reported in the 
literature.  The study is considered a success when the lower bound of the two-
sided Exact Clopper-Pearson mid-p 95% Confidence Interval for the Study 
Treatment Success is greater than or equal to 73.4%.  
 
 
 
 
Study 
Flowchart:  
  
2.0 
Postpartum Hemorrhage Background 
 
 Definition and Prevalence of Postpartum Hemorrhage 
Postpartum hemorrhage (PPH), or excessive blood loss after childbirth, is the leading cause of 
maternal mortality.  PPH is responsible for over a quarter of maternal deaths worldwide.1 In Africa and 
Asia, where most maternal deaths occur, PPH accounts for more than 30% of all maternal deaths.3  It 
is estimated that PPH afflicts 6% of women giving birth.2 Africa has the highest rate of PPH, with a 
Recruitment
Consent
Screening
PPH diagnosis 
/decision to use 
Jada System
Use of Jada 
System and data 
collection through 
discharge
Six-Week Follow-
up

           
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prevalence of 10.5% of women giving birth.2 Even developed countries are challenged by this life-
threatening complication of childbirth, causing 10.6% of maternal deaths in the United Kingdom, and 
12% of maternal deaths in the United States.4  
 
Although death is the most tragic event reported in obstetrics, severe maternal morbidity related to 
PPH such as surgical interventions including hysterectomy, disseminated intravascular coagulopathy, 
transfusions, and Intensive Care Unit (ICU) admissions, are more common than death.4-6 PPH can also 
be a cause of long-term severe morbidity, and approximately 12% of women who survive PPH will 
have severe anemia.12 Additionally, women who survive an event of severe PPH are significantly more 
likely to die in the year following the event.34 
 
Primary PPH, which is PPH that occurs within 24 hours after the birth of the baby, is the most 
common form of major obstetric hemorrhage. The most commonly accepted definition for primary 
PPH is the loss of 500 ml or more of blood from the genital tract within 24 hours after the birth of a 
baby. Severe primary PPH is commonly defined as loss of more than 1500 ml of blood within 24 hours 
after the birth of a baby. Alternative standards for defining and diagnosing PPH include changes in 
hematocrit, rapidity of blood loss and changes in vital signs.4,7-10   
 
It is difficult to predict who will develop PPH because most women who have PPH have no risk 
factors. Many deaths due to PPH could be prevented with timely diagnosis and intervention.  A blood 
loss of more than 1500 ml is usually considered life threatening and triggers a full complement of 
emergency measures to achieve resuscitation and hemostasis. It would seem appropriate that PPH 
protocols activate at much lower thresholds to prevent blood loss that requires drastic measures or 
becomes life threatening. 
 
Causes of Postpartum Hemorrhage 
PPH may be caused by uterine atony, injury to the birth canal, retained placenta, and coagulopathy, 
among other etiologies.   
 
Uterine atony, or suboptimal uterine contractions after childbirth, is the most prevalent cause, involved 
in 75% of primary PPH cases.8 Normally after delivery, the smooth muscle fibers of the uterus contract 
and constrict the blood vessels that serve the placental bed. If the uterus does not properly contract 
after delivery, these blood vessels are exposed to the cavity of the uterus, leading to uterine PPH. 
Atony may result from prolonged labor, prolonged use of uterotonic stimulants, over-distention of the 
uterus, infection, placental abnormalities, or bladder distention, but the majority (80%) of women with 
PPH due to uterine atony will have no risk factors.11  
 
Currently Available Treatment and Prevention Strategies 
Organizations and associations including the World Health Organization (WHO), International 
Confederation of Midwives, International Federation of Gynecologists and Obstetricians, American 
College of Obstetricians and Gynecologists, and Royal College of Obstetricians and Gynaecologists 
have released guidelines for PPH prevention and management.13,14,15-18  
 
The WHO guideline for the Active Management of the Third Stage of Labor (AMTSL) is 
recommended for all patients in order to prevent PPH.  The AMTSL guideline recommends the use of 
oxytocin, a uterotonic, for the prevention of PPH during the third stage of labor for all births.  In 
settings where skilled birth attendants are available, controlled cord traction may be used in vaginal 
births.  Postpartum abdominal uterine tone assessment is recommended to identify uterine atony prior 
to the occurrence of PPH. 
 

           
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If AMTSL does not prevent the occurrence of PPH, initial management guidelines include identifying 
the source of the PPH and implementing appropriate interventions based on the etiology. Manual 
removal of the placenta is indicated for a retained placenta; vaginal and vulvar lacerations need to be 
repaired in parallel to treating uterine bleeding.  Interventions to treat PPH due to atony generally 
proceed from less to more invasive.  Most guidelines first recommend the use of additional uterotonic 
agents, which cause the uterus to contract. These medications include oxytocin (Pitocin®), 
prostaglandin E1/misoprostol (Cytotec®), methylergonovine (Methergine®), prostaglandin 15-methyl 
F2α/carboprost tromethamine (Hemabate®), and prostaglandin E2/dinoprostone (Cervidil® or 
Prepidil®).13-16,24 All of these medications are available in the United States. Only oxytocin, 
methylergonovine, and carboprost tromethamine are approved by the US FDA specifically for PPH 
management. 
 
External uterine massage and bimanual uterine massage may also be used as first-line conservative 
treatments in conjunction with uterotonics. These techniques encourage uterine contractions that 
counteract atony and assist with expulsion of retained placenta or clots.  Initial PPH management also 
includes intravenous (IV) fluid therapy to expand volume and give access for parenteral medication.  
 
Some institutions use tamponade methods as a second line therapy if the uterotonics fail to take effect. 
These methods include uterine packing, the use of multiple Foley catheters or condom catheters (not 
FDA cleared for the treatment of PPH), or the use of a balloon tamponade device cleared specifically 
for PPH.  These methods create tamponade through compression of blood vessels, leading to the 
control of hemorrhage.  Although tamponade may occur, the expansion caused by the packing 
materials or balloon may interfere with the normal physiologic uterine retraction and constriction of 
placental bed vasculature that normally follows childbirth.  Thus, the uterine musculature can move 
back to its atonic state, causing blood loss to recur.  
 
If initial conservative management for PPH of uterine origin fails or is slow to take effect, invasive 
surgical procedures are indicated.  Surgical options include uterine curettage to ensure the removal of 
any residual products of conception, uterine de-vascularization procedures, uterine compression 
sutures, and, as a last resort, hysterectomy.13-16 Surgeries can increase the risk of infection, maternal 
morbidity and other complications, and they may eliminate or adversely affect future fertility and 
pregnancy.  
 
3.0 
Device Description 
 
Intended Use  
The Jada System is intended to provide control or reduction of postpartum uterine bleeding when 
conservative management is warranted. 
 
Jada System Description 
The Jada System is a 40 cm long intrauterine device made of silicone.  The device consists of an 
elliptical intrauterine loop collared by a donut shaped vacuum seal and a connecting tube that 
terminates in a male tubing slip vacuum port attachment (see Figure 1).  The loop has twenty pores 
directed towards the interior of the loop that are partially covered by a shield, which creates a channel 
to prevent plugging with tissue or clots.  The connecting tube has a seal port valve that can be attached 
to a syringe, allowing the vacuum seal to be filled with sterile IV fluid.  The various portions of the 
device are soft enough to reduce the chance of injury or perforation, but firm enough for easy insertion 
and smooth function without kinking. The Jada is designed to attach to sterile tubing and a regulated 
vacuum source with an in-line graduated vacuum collection canister.   

           
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Figure 1: Jada System 
 
Jada Overview 
The Jada System is inserted into a woman’s uterus transvaginally in women who have vaginal 
deliveries and trans-abdominally or transvaginally in women who have Cesarean sections (depending 
on whether PPH is diagnosed before or after the hysterotomy is closed). The shielded loop of 
perforated tubing is introduced in the uterine cavity. The vacuum seal is positioned in the upper 
vagina, against the external cervical os.  The male tubing slip vacuum port attachment can then be 
connected to sterile tubing, regulated vacuum source, and graduated vacuum collection canister.  See 
Figure 2.  
 
When the vacuum seal is filled with sterile IV fluid and the vacuum is turned on, the vacuum seal 
ensures that a vacuum can be created in the uterine cavity.   
 
 
Figure 2: Jada, properly positioned, prior to turning the vacuum on. 
 
Jada System 
Distal loop 
with pores 
Vacuum seal 
Vacuum Port 
Seal port valve for filling 
and evacuating vacuum 
l

           
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Once the vacuum is turned on, residual blood and clots from the PPH are suctioned through the 
vacuum tube.  After the residual materials are suctioned, the continued application of this vacuum 
force within the uterine cavity will cause the uterus to collapse upon itself, Figure 3. See Section 6.5 
for additional detail on the use of the Jada System. See the Instructions for Use for additional 
instruction on the use of the device.  
 
 
Figure 3: Negative pressure within the uterine cavity causing the uterus to collapse upon itself. 
3.3.1 Mechanism of Action 
The uterus is composed of a unique interlacing network of muscle fibers. Blood vessels that supply the 
placental bed pass through this latticework of uterine muscle, Figure 4. After delivery of the infant, 
when the placenta separates from the uterine wall, these fibers contract causing uterine retraction and 
constriction of these blood vessels. It is a physiologically efficient method for hemostasis. If the 
uterine muscle fibers do not contract as normal, PPH may occur.   
 
 
 
Figure 4: Muscular latticework basket weave diagram of the uterus 
 

           
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The Jada System facilitates an assisted physiologic restoration of normal postpartum uterine 
mechanisms. Jada establishes negative pressure within the atonic postpartum uterus, causing the uterus 
to collapse into and onto itself. The inner uterine walls press against one another, producing an 
immediate tamponade of the uterine cavity that causes rapid hemostasis. In this hemostatic state, the 
uterus is also stimulated to contract, and can retract down to its normal postpartum size and status 
without obstruction to optimal postpartum architecture.  Additionally, by generating tamponade and 
stimulating contractions without distension of the uterus, there is no risk of rupturing the scarred or 
sutured uterus when prior surgery or current Cesarean section is a risk factor. 
 
Prior Bench and Animal Testing 
Benchtop, safety, and animal studies have been performed to verify the functionality and performance 
of the Jada System.   
3.4.1 Benchtop Studies 
Functionality Verification was conducted to verify Jada is built to the specifications in the 
Manufacturing and Functional Specifications documents.  The shape integrity of the Jada was tested to 
verify that it would not collapse or break when being subjected to a vacuum of twice the recommended 
use.  The Flow Rate test verified that the Jada System facilitated a flow rate of at least 400 ml/min 
when an internal vacuum of 70 mm Hg was applied.  The connecting tube was tested to verify that it 
would facilitate a connection to a hospital-supplied collection vessel and vacuum line. The vacuum 
seal was tested to verify that it can withstand over-inflation to one and a half times its recommended 
size. The device was also tested in the presence of heavily clotted pig blood to verify that it can 
function within the presence of blood clots. 
3.4.2 Safety Studies 
Table 1: Safety Studies 
Test Category 
Tests Performed 
Testing Performed per Standard  
Pass/Fail 
Sterilization 
Validation 
Tests performed by SteriPro 
(through Sterigenics) to 
substantiate a 25 kGy dose 
and validate the 
effectiveness of Gamma 
batch release for sterilization 
of the Jada System. 
ANSI/AAMI/ISO 11137-2 
Pass 
Packaging and 
Shelf Life 
Validation 
Tests performed by Westpak 
to validate the packaging can 
withstand shipping & 
handling, various climates, 
and support a shelf life of 4 
years. 
Accelerated Aging 
ASTM F1980-07 
Pass 
Climatic Conditioning 
ASTM D4332-14 
Initial Manual Handling 
ASTM D5276-98 
Vehicle Stacking 
ASTM D642-00 
Loose Load Vibration 
ASTM D999-08 
Vehicle Vibration 
ASTM D4728-06 
Final Manual Handling 
ASTM D5276-98 
Gross Leak Detection 
(Bubble) 
ASTM F2096-11 
Seal Strength (Peel) 
ASTM F88/F88M-09 
Biocompatibility 
Validation 
Tests performed by NAMSA 
to validate the materials of 
the Jada System are 
biocompatible and 
nonirritating. 
 
Cytotoxicity Study 
Using the ISO Elution 
Method (1X MEM 
Extract) 
ISO 10993-5 
Pass 
ISO Maximization 
Sensitization Study—
Extract  
ISO 10993-10 

           
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ISO Vaginal Irritation 
Study 
ISO 10993-10 
Acute Systemic 
Toxicity – Extract 
ISO 10993-11 
3.4.3 Animal Studies 
There is no adequate animal model that duplicates PPH that is observed in humans; however, animal 
studies were conducted to test technical aspects of the device.  In the animal testing that was 
performed, Jada was evaluated in porcine and ovine bladders.  Testing supported the theory that 
vacuum could contract a sealed organ, thus, could theoretically reduce bleeding.   
 
First in Human Study Feasibility Study 
A First-in-Human (FIH) feasibility investigational study with Ethics Committee oversight 
was conducted at two clinical sites in Indonesia. The purpose of the study was to demonstrate the 
placement, function, and operation of the Jada System to meet its intended use to reduce or control 
PPH.   
 
Ten women were enrolled between July 2014 and February 2015.  None of the subjects presented with 
a retained placenta, uterine lacerations, uterine scarring, or for any conditions other than atonic post-
partum hemorrhage.  The Jada was successfully placed and activated in all ten subjects.  A vacuum 
force of 70 mmHg - 90 mmHg was used for treatment.  The average time from placement of the Jada 
to removal was 152.0 ± 111.7 minutes (range 60-390 minutes).  
 
Bleeding was controlled within two minutes for all ten subjects.  Evaluation of the primary clinical 
data safety endpoints determined that: 1) no safety issues were observed relative to the placement, 
insertion, or removal of the Jada, 2) there were no complications related to delayed arrest of blood 
loss, 3) there was no damage to the uterus, cervix, or vagina, and 4) no uterine inversion or folding 
events were observed during the Jada procedure. 
 
Risk Analysis 
A risk analysis has been performed in accordance with ISO 14971 for the Jada System.  The safety and 
risk profile of Jada have been further explored and substantiated in the FIH Feasibility study.  Based 
on the risk analysis and FIH study results, there is no expectation or current evidence to suggest that 
the risks will be increased with Jada as compared to commercially available tamponade devices.  Jada 
has the potential to work more quickly to treat PPH with less side effects.  Thus, the potential benefits 
of the device are expected to outweigh the risks.   
3.6.1 Potential Risks to Study Subjects  
Risks due to use of the Jada System and recommended actions are described below. 
Bleeding:  Bleeding may be observed due to mechanical injury to blood vessels or tissue in the area 
where the Jada System is inserted and deployed.  If bleeding due to the device is suspected, the 
Investigator should remove the device and repair the injured area, as indicated.   
Pain / Cramping:  Subjects may experience pain or discomfort during the intervention and possibly 
post-intervention for a short duration of time.  Non-steroidal anti-inflammatory or other analgesic 
medication may be provided for relief.    
Perforation of or injury to uterus, fallopian tubes, and adjacent structures: Perforation or injury to the 
vagina, uterus, fallopian tubes, or adjacent tissue is a possible risk during insertion of any foreign 
object into the uterus.  If perforation due to Jada is suspected, the Investigator should remove the 
device and evaluate the subject for further treatment.  

           
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Infection: Infection is a possible complication following the placement of any foreign object into the 
uterus.  If infection due to Jada is suspected, the Investigator should evaluate the subject and provide 
treatment (e.g. antibiotics) as indicated.   
 
Failure to stop PPH: Patient monitoring is an integral part of managing PPH. Signs of deteriorating or 
non-improving condition should lead to a more aggressive treatment of uterine bleeding. There is a 
risk that the use of Jada will not achieve its intended goal of stopping the PPH; therefore, other 
treatments may be required. It is noted that while Jada is designed to stop PPH, it does not treat the 
effects of blood loss, so is not a replacement for fluid resuscitation and should be used along with 
proper treatment for blood loss (i.e., transfusions).  
 
Unknown Risks:  As with any investigational device, there may be risks that are currently unknown or 
unanticipated. 
 
Inconvenience: There may be added inconvenience to the study subject for participating in the study. 
The potential for inconvenience is thought to be very minimal for this study as there are no additional 
requirements for visits outside of standard of care for study subjects.  
 
Loss of confidentiality: There may be loss of confidentiality of a subject’s study-related Protected 
Health Information (PHI) due to participation in the study. The investigational site and study sponsor 
will do everything possible to limit this risk by storing research records in secure areas and limited 
access to these records.  
3.6.2 Risk Detection and Mitigation 
Several precautionary measures have been built into the investigational protocol to protect the study 
subjects and to detect any potential adverse effects.   
 
• 
Inclusion/exclusion criteria were identified to help assure that any study subject who may be at 
increased risk for an adverse event is not enrolled in the study.  Also, study subjects will be 
observed during and following the intervention to assure that any acute adverse events are 
detected in a timely manner so that proper medical treatment can be initiated.  Subjects will be 
followed at 6 weeks following the intervention in order to capture other possible intervention-
related adverse events that do not manifest immediately.  
 
Potential Benefits of the Intervention  
The potential clinical benefits include: 
• 
Treatment that mirrors the normal postpartum physiology of the body, which may result in a more 
rapid control of hemorrhage. 
• 
Less invasive device than commonly used surgical interventions. 
• 
Avoidance of the use of some uterotonics or shortening duration of use that have more systemic 
adverse effects. 
• 
No outward physical pressure on a scarred or sutured uterus unlike other commonly used 
tamponade devices. 
• 
Ability to measure blood loss after initiation of treatment due to the use of the in-line graduated 
canister.  
 
If Jada proves effective and safe in treating PPH, there are also larger benefits expected for global 
health care systems: 

           
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• 
Control PPH rapidly, resulting in reduced costs 
• 
Decrease physician time for the intervention and monitoring 
• 
Reduce use of operating rooms or ICUs and decrease length of hospital stays  
• 
Lower cost product than currently available balloon tamponade devices, allowing Jada to 
significantly benefit emerging countries. 
4.0 
Study Objectives 
 
Purpose of the Study  
The purpose of this Pivotal Study is to evaluate the safety and effectiveness of the Jada System in the 
control and reduction of primary PPH. 
 
Study Endpoints  
4.2.1 Primary Effectiveness Endpoint  
Control of postpartum hemorrhage, defined as the avoidance of non-surgical, second line or surgical 
intervention to control uterine hemorrhage after the use of the Jada System per the Instructions for 
Use. 
 
Non-surgical, second line procedures include uterine balloon therapy, uterine packing, or uterine artery 
embolization.  Surgical intervention includes procedures such as uterine arterial ligation, uterine 
compression sutures or hysterectomy. 
 
Note: Continuation of the administration of uterotonics concomitant with and post Jada use is standard 
of care as long as such use does not exceed the maximum dose of the drug and does not constitute 
failure of the primary effectiveness endpoint. 
4.2.2 Primary Safety Endpoint 
Safety: Incidence, severity and seriousness of device-related Adverse Events. 
4.2.3 Secondary Endpoints  
1. Time to control hemorrhage, defined as the time from turning on the vacuum source until the time 
the first of any of the following occurs:  
• 
there is no blood being collected in the tubing or canister, or 
• 
the blood loss is observed as leveled off in the canister, or  
• 
blood loss is at a rate of < 500 ml in 24 hours.  
2. Rate of surgical intervention required to control PPH after Jada use. 
3. Rate of non-surgical intervention required to control PPH after Jada use. 
4. Assessment of device usability as reported by the clinician using a dedicated data collection form. 
5. Rate of blood product transfusion required after Jada use, and number of transfusion units when 
administered. 
 
 
Overall Study Success 
A thorough review of all known publications reporting on the use of the Bakri Balloon to treat PPH 
was performed.  A meta-analysis methodology was used to aggregate the studies and provide a 
numerical estimate of the overall Treatment Success Rate. Based on a random effects model, the 
estimated pooled proportion of subjects who reached hemostasis (i.e., control of uterine hemorrhaging) 

           
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following Bakri Balloon (or equivalent) treatments was 82.0% (95% CI: 73.4% to 89.2%). See the 
Clinical Evaluation Report (G150265, Attachment H, pages 337-382). 
 
The primary effectiveness objective of this Pivotal Study is to show that the observed Treatment 
Success Rate is not worse that the rate reported in the literature.  The study is considered a success 
when the lower bound of the two-sided Exact Clopper-Pearson mid-p 95% Confidence Interval for the 
Study Treatment Success is greater than or equal to 73.4%.  
 
5.0 
Study Design  
 
Overview 
This study design is prospective, single-arm, literature-controlled, and multi-center. Since this is a 
literature-controlled study, meta-analysis methodology was used to establish target endpoints which 
will demonstrate the safety and effectiveness of the Jada System.  See the Clinical Evaluation Report 
(G150265, Attachment H, pages 337-382). 
 
Site Selection 
The study will be conducted at no less than five and no more than twenty sites, which may include both 
U.S. and O.U.S sites.  Site selection will be conducted in accordance with sponsor Standard Operating 
Procedures.  If O.U.S. sites are enrolled, they will comply with FDA’s February 2018 guidance titled 
“Acceptance of Clinical Data to Support Medical Device Applications and Submissions, Frequently 
Asked Questions, Guidance for Industry and Food and Drug Administration Staff.” 
 
 
Study Training  
The training program for sites participating in the study will include the following: 
1. 
Didactic training; 
2. 
Hands-on training; 
3. 
Investigator Training Certification Quiz; 
4. 
Procedure Guide Poster. 
 
All investigators will be required to undergo both hands-on training and didactic training and 
successfully pass the Investigator Training Certification Quiz, which will be administered after the 
training is complete.  The trainee will be considered to have passed the Investigator Training 
Certification Quiz once all questions have been answered correctly, which may involve a retake of the 
quiz.   
 
Didactic Training 
The didactic training will be performed by Alydia Health staff that are qualified to perform the 
training.  The didactic training will be performed either in person or via videoconference.   
 
Hands-On Training 
Hands-on training will be provided by qualified persons who are familiar with the Jada System and 
PPH. Trainees will use demonstration samples of the Jada System in bench models built by Alydia 
Health to simulate anatomy in both transvaginal placement and transabdominal placement.  This 
clinical experience simulation is intended to ensure operators master the Jada procedural steps prior to 
live study subject procedures.  Trainees will be required to independently and individually demonstrate 
successful deployment of a minimum of one Jada System in each model before they are approved to 
use the device.  Successful deployment is defined as following all of the procedural steps in 

           
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accordance with the Instructions for Use without prompting or correction by the trainer in the 
transvaginal model, and successfully completing the device positioning steps in the transabdominal 
model also without prompting or correction by the trainer.  This may require more than one 
deployment attempt. 
 
Procedure Guide Poster 
Finally, as a post-training reminder and reference, each site is provided with a Procedure Guide Poster, 
which serves as a quick reference guide for the procedure.   
 
Study Population  
5.4.1 
Number of Subjects and Sample Size Calculation 
Up to 107 subjects will be enrolled in the study to ensure that 96 subjects are available for the analysis 
of the primary effectiveness endpoint.  Sites are expected to enroll a minimum of 5 subjects.  Site 
enrollment will be capped at 30% of the total expected enrollment, such that no site will enroll more 
than 32 subjects. 
 
The study is powered to show that the Treatment Success Rate among the Jada subjects is not inferior 
to the Treatment Success Rate derived from a meta-analysis performed using all known publications 
reporting on the use of the Bakri Balloon (and equivalents) to treat PPH.   
 
Based on a random effects model used in the meta-analysis, the estimated pooled proportion of 
subjects who reached hemostasis (i.e., control of uterine hemorrhaging) following Bakri Balloon 
treatments was 82.0% (95% CI: 73.4% to 89.2%). See the Clinical Evaluation Report (G150265, 
Attachment H, pages 337-382). 
 
Non-inferiority will be achieved when the lower bound of the Exact Clopper-Pearson mid-p 95% 
Confidence Interval for the Study Treatment Success Rate is greater than or equal to the lower bound 
of the 95% Confidence Interval of the Treatment Success Rate derived in the meta-analysis, or 73.4%.  
That is: 
 
Statistical Hypothesis: 
H0: πJada < πLiterature CI LB vs H1: πJada > πLiterature CI LB 
where πJada is the Treatment Success Rate for Jada treated subjects and 
πLiterature CI LB is the lower bound of the 95% Confidence Interval for the 
Treatment Success Rate derived from the meta-analysis of the Bakri 
Balloon Literature. 
Statistical Methodology: 
Confidence Interval for πJada 
Expected πJada: 
0.82 
Half-width of 95% CI: 
0.086 
Confidence Level: 
Two-sided 95% 
Minimum Sample Size: 
n = 96 evaluable subjects 
Statistical Power: 
 
0.806 that the lower bound will be greater than or equal to 0.734 
 
With 96 evaluable subjects, there is an 80.6% probability that the lower bound of the observed Exact 
Clopper-Pearson mid-p two-sided 95% confidence interval will be expected to be greater than 0.734 
when the Jada Treatment Success is expected to be 82%. (Calculated using SAS v9.4 PROC POWER.) 

           
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For safety, with 96 subjects treated with Jada, there is a 95% chance of observing at least one adverse 
event when the underlying incidence of the event is at least 3.1%.   
 
To account for up to 10% of the subjects withdrawing early or not having data available for the 
analysis of the primary effectiveness endpoint, a total of 107 subjects will be enrolled. 
 
5.4.2 
Source of Subjects  
Subjects will be identified and recruited from inpatient and outpatient facilities affiliated with or at 
study sites. Any recruitment materials used that are intended for use with patients must be approved by 
the Sponsor and the reviewing IRB prior to use.  
5.4.3 
Inclusion/Exclusion Criteria  
All patients must be carefully screened against all inclusion and exclusion criteria prior to enrollment 
in the study. Each Jada System will be shipped with a source worksheet listing all eligibility criteria, 
which should be used to ensure compliance with study eligibility criteria during subject enrollment.  
Inclusion Criteria:  
1. Adult Female, 18 years of age or older at time of consent. 
2. Able to understand and provide informed consent to participate in the study. 
3. Diagnosis of PPH with suspected atony within 24 hours after vaginal or c-section delivery. 
4. EBL, determined when investigator is ready to have the Jada peel pack opened: 
Vaginal delivery: 500 – 1500 ml EBL or 
C-section delivery 1000 – 1500 ml EBL 
5. Failed first-line intervention of uterotonics and uterine massage/bimanual uterine massage to stop 
bleeding.  
Note:  Uterotonic administration may continue concomitant with and post Jada use, as long as 
such use does not exceed the maximum dose of the drug. 
 
Exclusion Criteria:  
 
1. EBL >1500ml, to be determined when investigator is ready to have the Jada peel pack opened. 
2. Delivery at a gestational age < 34 weeks. 
3. For C-sections: Cervix < 3 cm dilated before use of Jada.  
4. PPH that the investigator determines to require more aggressive treatment, including any of the 
following: 
a) hysterectomy; 
b) b-lynch suture; 
c) uterine artery embolization or ligation; 
d) hypogastric ligation. 
5. Known uterine anomaly. 
6. Ongoing intrauterine pregnancy. 
7. Placenta abnormality including any of the following: 
a) known placenta accreta; 
b) retained placenta with known risk factors for placenta accreta (e.g. history of prior uterine 
surgery, including prior c-section and placenta previa); 
c) retained placenta without easy manual removal. 
8. Known uterine rupture.  
9. Unresolved uterine inversion. 

           
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10. Subject has undergone intrauterine balloon therapy or uterine packing for tamponade treatment of 
this PPH prior to use of Jada. 
11. Current cervical cancer. 
12. Current purulent infection of vagina, cervix, uterus.  
13. Diagnosis of coagulopathy. 
5.4.4 Subject Withdrawal and Termination 
Subjects will be advised that they may voluntarily withdraw from the study at any time and will be 
instructed to notify the Investigator immediately if they choose to withdraw.  A subject may choose to 
withdraw for any reason and is not obligated to reveal reason(s) for withdrawal.  Any data contributed 
up to the point of withdrawal will be included in the analyses.  In addition, any adverse events that are 
ongoing at the time of the subject’s withdrawal will be marked as such on the Adverse Event case 
report form. Subjects will be followed until the adverse event is resolved or is not expected to change.  
 
Subjects may also be involuntarily terminated from the study by the Investigator if the Investigator 
believes it is in the best interest of the subject. This may occur if the investigator believes more 
aggressive treatment is necessary prior to the use of Jada. This may also occur if the Investigator 
decides to abort the treatment with Jada after it is inserted. If a Jada is inserted in the subject but 
treatment is aborted thereafter, the subject will be followed for six weeks.  
 
Duration of Study and Subject Participation 
All eligible study subjects who are enrolled in the study will be expected to continue participation in 
this clinical study for six weeks following the Jada intervention, except as provided in the section on 
subject withdrawal and termination.  For this study, “enrolled” is defined as: 1) signing the Informed 
Consent Form and 2) meeting the inclusion/exclusion criteria.  
 
The literature cites PPH prevalence rates ranging from 2% (severe PPH) to 5% (primary PPH) in the 
United States. This would mean 2000 to 5000 deliveries would be needed to reach the target 
enrollment of 107 subjects. Consequently, it is anticipated that it will take approximately 12-18 
months to screen, enroll, intervene, and follow-up all 107 subjects.    
 
Justification for Study  
A feasibility clinical study of the Jada System has been completed with encouraging results. See the 
Clinical Evaluation Report (G150265, Attachment H, pages 337-382).  In this feasibility study, Jada 
was used in a limited population of women who had failed first line conservative therapy.  This study 
excluded subjects delivering by Cesarean section and subjects with other major identifiable causes of 
PPH other than atony. This conservative subject selection process was deliberately chosen to reduce 
the variance in the treated population in order to clearly demonstrate the device’s mechanism of action 
and allow safety to be elucidated.  In all ten subjects, PPH ceased within two minutes.  The Jada 
System was left in place for up to 6.5 hours.  None of the subjects experienced a device-related 
adverse event. 
 
Subsequent to this Feasibility Study, clinical use of vacuum via uterine cannula (different device than 
the Jada) to create uterine tamponade was reported by Ram et al in 2014.25 Sixteen women who had 
vaginal deliveries and four women who underwent Cesarean sections were included in the study. All 
women received 10 units of oxytocin at the appearance of the baby’s anterior shoulder, 5 units of 
intravenous oxytocin after the delivery of the placenta, and then uterine massage. Carboprost 125 mcg 
was also given when the bleeding did not stop. All 20 women were then administered the uterine 
vacuum retraction system via rigid cannula and vacuum forces of 650 mmHg for 10 minutes at a time. 
Complete cessation of bleeding which was associated with contraction and firm retraction of the uterus 

           
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was observed in all women within 4 minutes of initiation of the procedure. The clinical outcomes for 
the vaginal deliveries and Cesarean sections were comparable.  No adverse events were reported. 
 
These early studies demonstrated the safety and initial effectiveness of the use of a vacuum to create 
uterine tamponade and treat postpartum hemorrhage.  This Pivotal Study is designed to gather more 
data demonstrating the safety and effectiveness of the Jada System in a larger patient population.  
Meta-analysis methodology was used to establish target endpoints which will demonstrate the safety 
and effectiveness of the Jada System; as such, the resulting design is a literature-controlled study 
design.  
6.0 
Study Procedures 
 
Subject Recruitment  
Participants will not be recruited until the Institutional Review Board governing their treatment facility 
has approved the study.   
 
The Investigator may begin recruiting participants at any time prior to the diagnosis of PPH in 
accordance with the requirements of the following section, Subject Consent.  The supplied short 
Patient Study Brochure, the PEARLE Study Poster, or the Patient Study Information Video can be 
used at this point to introduce the study to all potential participants (provided these recruitment 
materials have been approved by the IRB at the site), prior to issuing the lengthier informed consent 
form. Use of the brochure, study poster and video information tools are optional.    
 
Subject Consent  
Principles of Informed Consent 
As stated by US FDA,1 “To many, the term informed consent is mistakenly viewed as synonymous with 
obtaining a subject’s signature on the consent form. FDA believes that obtaining a subject’s oral or 
written informed consent is only part of the consent process. Informed consent involves providing a 
potential subject with adequate information to allow for an informed decision about participation in 
the clinical investigation, facilitating the potential subject’s comprehension of the information, 
providing adequate opportunity for the potential subject to ask questions and to consider whether to 
participate, obtaining the potential subject’s voluntary agreement to participate, and continuing to 
provide information as the clinical investigation progresses or as the subject or situation requires. To 
be effective, the process must provide sufficient opportunity for the subject to consider whether to 
participate. (21 CFR 50.20.) FDA considers this to include allowing sufficient time for subjects to 
consider the information and providing time and opportunity for the subjects to ask questions and have 
those questions answered. The Investigator (or other study staff who are conducting the informed 
consent interview) and the subject should exchange information and discuss the contents of the 
informed consent document. This process must occur under circumstances that minimize the possibility 
of coercion or undue influence.” 
 
Study Requirements 
Upon determination of subject eligibility (preliminary completion of study entry criteria), the patient 
will have the opportunity to discuss any risks, benefits, alternative therapies, and the study 
requirements with the Investigator prior to signing the informed consent document. Signed informed 
consent shall be obtained from each study subject prior to use of the investigational device.  
                                                 
1 Informed Consent Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors, Draft issued July 
2014 
 

           
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Consent Timing 
Given the potential for duress, the timing for obtaining informed consent from women undergoing 
labor and delivery raises unique considerations.  As such, considerations and requirements for timing 
of obtaining informed consent are discussed below. 
 
Informed consent for this study can be obtained during several different phases of interaction with the 
patient:   
Phase 1:  At any antenatal obstetrical office visit prior to the onset of labor 
Phase 2:  After hospital admission, but before the onset of labor, including the following: 
• 
Women making an antenatal visit at the hospital 
• 
Women admitted for labor induction 
• 
Women with ruptured membranes, but who are not in labor 
Phase 3:  After the onset of labor, but before the diagnosis of PPH 
 
In all 3 phases, the patient must be provided adequate time to review the informed consent form and 
consider whether or not to participate.  For women considered high risk for PPH, it is ideal to obtain 
informed consent during Phase 1.  In order to avoid undue anxiety for those women who are not 
considered at high risk, consent can be obtained later, upon hospital admission, when many possible 
although unlikely interventions are routinely discussed.   
 
During Phase 3, there is an increased likelihood that the woman will be under periods of duress.  As 
such, the following safeguards will be applied to informed consent that is obtained during Phase 3. 
 
Informed consent will not be obtained when any of the following apply: 
1. The patient has been diagnosed with PPH. 
2. The patient has arterial bleeding requiring surgical exploration or angiographic embolization. 
3. The patient requires immediate life-saving hysterectomy. 
4. The patient is in the second stage of labor.  
5. The patient is experiencing a contraction. 
6. The patient is experiencing pain or discomfort that prevents a lucid discussion of the elements of 
the informed consent form. 
7. The patient is undergoing a gynecological examination. 
8. The patient is distracted by the placement or adjustment of fetal or labor monitoring devices. 
9. The patient is undergoing administration of an epidural regional anesthetic or spinal anesthetic. 
10. The study Investigator believes that the patient’s level of mental and/or physical stress prevents a 
lucid discussion of the elements of the informed consent form. 
 
The patients will be informed by the Investigator or Investigator’s designee that they are free to refuse 
participation in this research study.  If they elect to participate, it will be made clear that they may 
withdraw from the study at any time without prejudicing further care.  
 
The Investigator or the Investigator’s designee will inform patients that their medical records will be 
subject to review by the sponsor and appropriate regulatory bodies.  This information will be used 
during the analysis of the results of the clinical study, but the patients’ identities will be treated as 
confidential.  Patients will be assigned a unique study subject code that will not reveal the patient’s 
identity, and this code will be used on all data and data collection forms during the study period.  
 
The Investigator or their designee will explain the conditions of the study, giving the patient sufficient 
time to ask questions and to consider whether or not they want to participate.  If the patient agrees, 
they shall be given an approved consent form for signature and date.  A copy of the consent form will 

           
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be given to the patient.  The original consent forms will be kept by the Investigator and will be subject 
to review by the sponsor or a representative of the sponsor, and by the appropriate regulatory bodies. 
 
If the patient signs the informed consent form, the site must place a PEARLE Consent ID bracelet on 
their wrist to indicate that they have been consented.  
 
 
Figure 5: PEARLE Consent ID Bracelet 
 
 
Subject Pre-Enrollment Screening 
All patients must be screened for all inclusion and exclusion criteria prior to being enrolled in the 
study.  
 
At any time during the consent process or after, if the subject is known to screen fail the study for any 
inclusion or exclusion criterion, the process of working toward enrollment of that subject should cease. 
This includes any information that becomes known from subject interview, subject history, or 
examination at any point after admission. Once a person is known to not fulfill any criterion, the 
identification of their consent should be removed. For example, if they have a PEARLE Consent ID 
bracelet on, it should be removed from their wrist.  
 
Subject Enrollment 
The Investigator should consider all possible causes of bleeding, including evaluating for lacerations, 
retained placenta, broad ligament and vaginal hematomas, uterine rupture, and other causes requiring 
different treatment pathways.  First line therapies should be attempted in accordance with the 
institution’s PPH protocol.  After first line therapies have been attempted and failed, the Investigator 
will make the decision to use Jada to attempt control or reduction of PPH.  The subject will be 
considered “enrolled” after she: 1) signs the Informed Consent Form and 2) meets the 
inclusion/exclusion criteria. 
 
Intervention 
The Investigator will use Jada in conjunction with the device’s Instructions for Use that is included 
with every device.  Following the steps of the IFU and according to their training, the Investigator will 
place the Jada intrauterine loop into the uterus.  For vaginal deliveries, the device will be placed 
transvaginally; for Cesarean deliveries, the device will be placed trans-abdominally or transvaginally 
(if the hysterotomy was closed first).  The vacuum seal will be filled with 60 ml sterile IV fluid.  
Vacuum forces will be applied to suction residual blood and debris.  Once the residual blood is 
removed, the pressure gradient from the vacuum creates a uniform mechanical stimulus on the uterus, 
causing it to collapse into and onto itself.  At that time, tamponade occurs and hemorrhage is expected 
to be controlled.  Vacuum forces will be maintained for at least one hour (from the time hemorrhage is 
controlled) until the subject is stable or until the Investigator determines that hemorrhage was not 

           
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controlled and further intervention is needed. If any further intervention is required to treat the PPH, it 
will be reported on the Procedure case report form, capturing details on the intervention. 
 
Once the Investigator detaches the tubing from the device or “zero’s” the vacuum source and the seal 
is emptied of the fluid, the device should remain in place and taped to the patient’s inner thigh for at 
least 30 minutes, provided the subject is stable and there is no medically valid reason to remove the 
device. The 30-minute minimum observation period allows for the Investigator to re-initiate treatment 
should the uterus return to an atonic state with abnormal bleeding.  
 
If the subject remains stable and the PPH does not return for 30 minutes, then the device can be 
removed and decommissioned (cut up) prior to final disposal. Device pieces should be discarded in 
accordance with hospital biohazardous waste policies. If there was a device malfunction, the 
Investigator or designee should wrap the device in a biohazardous disposal bag and contact Alydia 
Health for further instructions to return the device for evaluation.  
 
Other standard of care medical evaluation and care must be ongoing during the use of the Jada System. 
If it is determined that blood products must be administered, then the Investigator should follow the 
local protocol to do so.  
 
Post-procedure Follow-up 
After removal of Jada and before subject discharge from the hospital, additional data collection is 
required.  Information about the following will be collected on case reports forms: 
● Physical Examination, including limited Pelvic Examination 
● If done, CBC and coagulation panel results 
● Clinician Assessment of Device Usability 
● Assessment of any adverse events that occur from the beginning of device use to discharge 
 
Six-week Follow-up 
A study follow-up assessment will occur at the subject’s normal 6-week postpartum follow-up visit.  
The following assessments will be performed: 
• 
Physical Examination, including limited Pelvic Examination 
• 
Assessment for any adverse events 
 
Note: If a patient is unable to return for their normal 6-week postpartum visit after three documented 
attempts to complete the visit, follow-up should occur via phone to gather data related to adverse events 
from the discharge through this single follow-up time point. 
 
Summary Table of Clinical Assessments 
The schedule of clinical assessment is outlined in Table 2.  
 
Table 2: Clinical Assessment Schedule  
Procedure/Assessment 
Baseline 
Jada Procedure  
through discharge 
 
6-Week 
 Follow-up 
42 days ± 14 days 
Screening for inclusion / 
exclusion 
√ 
 
 
Informed Consent and HIPAA 
authorization 
√ 
 
 
Enrollment 
 
√ 
 

           
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Demographics, history and 
delivery data collection 
√ 
 
 
General exam  
√ (after 
delivery but 
prior to PPH 
dx) 
√ (after Jada use and prior to 
discharge) 
√ 
Vital Signs (at admission) 
√ 
 
 
CBC / Coag Panel 
√* (at 
admission) 
√* (after Jada use and prior to 
discharge) 
 
Jada procedure and endpoint 
assessment 
 
√ 
 
Investigator assessment of device 
usability  
 
 √ 
  
Adverse Event assessment 
 
√ 
√ 
Assessment of medications that 
may affect bleeding 
√ 
√  
 
Study exit 
 
 
√ 
 
√* If an Investigator deems it medically important to conduct the CBC or coagulation panel, the results of these should 
be recorded in the Baseline and Post-Procedure Through Discharge case report forms. 
 
7.0 
Safety and Adverse Events 
 
Definitions 
7.1.1 Adverse event 
An adverse event is any untoward medical occurrence (i.e., any unfavorable and unintended sign, 
including abnormal laboratory findings, symptom, or disease) in a clinical investigation subject after the 
subject enrolls in this study.  Adverse events will be categorized as serious and non-serious, device-
related and non-device-related, and anticipated and unanticipated.  
7.1.2 Adverse device effect 
An adverse device effect (ADE) is an AE related to the use of the device, including AEs resulting from 
insufficient or inadequate instructions for use, installation or operation, or any malfunction of the 
investigational medical device, use error or from intentional misuse of the medical device.  
7.1.3 Device deficiency 
A device deficiency is an inadequacy of device related to its identity, quality, durability, reliability, 
safety, or performance, such as malfunction, misuse, or use error and inadequate labeling. 
7.1.4 Device failure 
A device failure is a failure of the device to perform or function as intended, including any deviations 
from the performance specifications or intended use. 
7.1.5 Device malfunction 
A device malfunction is a failure of the device to meet its performance specifications or otherwise 
perform as intended when used in accordance with the Instructions For Use. 
7.1.6 Device misuse 

           
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A device misuse occurs when the Investigator uses the device in a manner that is contradictory to the 
Instructions For Use. A device misuse will not be considered a malfunction. 
7.1.7 Device-related adverse event 
A device-related adverse event is any AE for which a causal relationship between the device and the 
AE is at least a reasonable possibility (i.e., the relationship cannot be excluded).  
7.1.8 Near incident 
A near incident is any malfunction or deterioration in the characteristics and/or performance of the 
device (an ADE) which might have led to death or serious deterioration in health. The incident occurred 
and is such that if it occurred again, it might lead to death or serious deterioration in health. 
7.1.9 Serious adverse device effect 
An ADE that results in any of the consequences of a serious adverse event “SAE”. The term serious 
adverse device effect (SADE) is synonymous with “incident”. 
7.1.10 Serious adverse event (SAE) 
Any adverse event that meets at least one of the following criteria (a—f): 
a. Results in death. 
b. Is life-threatening. 
 
The term ‘life-threatening’ in the definition refers to an event in which the subject was at risk of 
death at the time of the event, it does not refer to an event which hypothetically might have caused 
death if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization. 
 
A hospitalization or prolongation of hospitalization will not be regarded as an SAE if at least one of 
the following exceptions is met: the admission is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study) OR the admission is not associated with an AE (e.g., social 
hospitalization for purposes of respite care).  However, it should be noted that invasive treatment 
during any hospitalization may fulfill the criterion of ‘medically important’ and as such may be 
reportable as an SAE dependent on clinical judgment.  In addition, where local regulatory 
authorities specifically require a more stringent definition, the local regulation takes precedence. 
d. Results in persistent or significant disability / incapacity. 
 
Disability means a substantial disruption of a person’s ability to conduct normal life’s functions. 
e. Results in fetal distress, fetal death or a congenital abnormality or birth defect. 
f. 
Is considered an important medical event that jeopardizes the health of the subject or requires 
surgical intervention to prevent one of the outcomes listed above as judged by the Investigator. 
7.1.11 Unanticipated adverse device effect 
An unanticipated adverse device effect (UADE) is any SADE on health or safety or any life-
threatening problem or death caused by, or associated with, a device, if that effect, problem, or death 
was not previously identified in nature, intensity, or degree of incidence in the investigational plan or 
application or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
 
Classifications for Adverse Event Assessment 
All AEs from beginning of device use to subject termination will be assessed and documented by the 
Investigator according to the categories detailed below: 
7.2.1 Seriousness 

           
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For each AE, the seriousness must be determined according to the criteria given in section 7.1 
(Definitions). 
7.2.2 Severity 
The severity of an AE is classified according to the following categories: 
• 
Mild 
• 
Moderate 
• 
Severe 
7.2.3 Causal relationship 
The assessment of the causal relationship between an AE and the device or procedure is a clinical 
decision based on all available information at the time of the completion of the AE case report form. 
The assessment is based on the question whether there was a “reasonable causal relationship” to the 
procedure and/or device. 
 
Possible responses to causal relationship are “related”, “possibly related”, or “not related”. 
• 
An assessment of “not related” would include (1) the existence of a clear alternative explanation 
(e.g., the subject develops a local infection from an unrelated laceration) or (2) non-plausibility 
(e.g., the subject is struck by an automobile when there is no indication that the device caused 
disorientation that may have caused the event). 
• 
An assessment of “possibly related” indicates that there is a reasonable suspicion that the AE is 
associated with the procedure and/or device, but not definitively so. 
• 
An assessment of “related” indicates that the AE is very likely associated with the procedure 
and/or device. 
 
Important factors to be considered in assessing the relationship of the AE to the device or procedure 
include (1) the temporal sequence from the procedure—the event should occur after the procedure is 
initiated, (2) underlying, concomitant, intercurrent diseases—each event should be evaluated in the 
context of the natural history and course of the procedure and any other medical conditions the subject 
may have, and (3) concomitant medications or procedures—any drugs the subject is taking or the 
additional procedures the subject receives should be examined to determine whether any of them may 
be suspected to cause the event in question. 
7.2.4 Anticipated 
A list of anticipated adverse events is in Section 3.6.1.   For this study, the applicable reference 
documents are this protocol and the Clinical Evaluation Report (G150265, Attachment H, pages 337-
382). Classification of AEs as anticipated and unanticipated will be determined by the Investigator 
using the reference documents.    
 
Assessments and documentation of adverse events 
The Investigator must collect all AEs for each subject from the time of enrollment through the end of 
subject study participation, whether or not deemed related to the investigational device or procedure. A 
hospitalization or surgical procedure that was scheduled prior to subject enrollment should not be 
deemed an adverse event. All AE data will be recorded on the AE case report form.  The Investigator 
must make an assessment and document it on the AE case report form. The Independent Medical 
Monitor will adjudicate all reported adverse events. 
 
All AEs will be followed through resolution or until the AE is not expected to change.  The subject 
will be referred to his or her primary care physician for any ongoing medical issues continuing beyond 
the completion of the study.  

           
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Reporting of serious adverse events and near incidents 
The definition of SAE is provided in Section 7.1. These include device deficiencies that may have led 
to a SAE if a) suitable action had not been taken or b) intervention had not been made or c) if 
circumstances had been less fortunate.  
 
Notification to sponsor: All serious adverse events (whether or not considered device-related) must be 
reported immediately (within 24 hours) to: 
 
Kathryn D. Wine, MPH 
Clinical Operations 
415.990.4104 
Kathryn@alydiahealth.com 
If e-mail receipt is not confirmed, please call to provide notification. 
 
Notification of the IRB: Notification of the IRB about all relevant events will be performed by the 
Investigator according to all applicable requirements. 
 
Device Deficiencies 
The Investigator must document all device failures, malfunctions, and use errors, including the 
assessment whether the event is considered a near incident (ADE) using the Device Deficiency case 
report form.  The case report form must be faxed or emailed to the Sponsor within 24 hours of 
Investigator knowledge of the event.  If a device malfunctions, the Investigator must contact the 
Sponsor to determine if the device should be returned. 
 
Study Termination 
If new information is discovered during the study that indicates that the device or intervention provides 
an unreasonable risk to subjects, study enrollment will be suspended or discontinued.  Enrollment will 
only be resumed once the risk has been appropriately mitigated and authorization to resume is obtained 
from FDA and the reviewing IRB.  Regardless of ability to resume the study, all treated subjects will 
be followed as required by the protocol (6 weeks post-intervention). 
 
The study or any clinical study site may also be halted or terminated early by the Sponsor for business 
reasons.   
 
8.0 
Data Collection, Reporting and Quality Assurance 
 
Case Report Forms 
Case report forms will be used to record demographic, intervention, and follow-up data, as well as any 
protocol deviations, adverse events, or device malfunctions that may occur during the study period.   
 
Protocol Deviations 
A Protocol Deviation Form must be completed for each study protocol deviation (e.g., failure to obtain 
informed consent, enrolling a subject who does not meet inclusion/exclusion criteria2, not performing 
                                                 
2 There may be times when the pre-treatment EBL is re-estimated after Device use. If the re-estimation 
of the pre-treatment EBL is greater than the maximum EBL allowed for study entry by ≤ 20% (i.e. the 
re-estimate was < 1800 ml), then the site is not required to report a protocol deviation to the EBL 
 

           
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required testing, missed follow-up window, etc.).  The Investigator must notify the Sponsor and the 
reviewing IRB of any deviation from the investigational plan that was done to protect the life or 
physical well-being of a subject (medical emergencies).  Such notice should be given within 24 hours 
after the emergency occurred.   
 
Efforts to Minimize Data Loss 
If a subject fails to comply with the follow up evaluations, the study site must attempt to contact the 
subject at least three times, including once as a registered letter.  In order to minimize loss to follow-
up, during the hospitalization, the study coordinator will request that the subject provide names and 
contact information of two individuals that have a close relationship with the subject.  The contacts 
will be utilized in the event that the subject relocates or cannot be reached by mail or telephone.  This 
information will be treated as confidential and for use by the investigative site only. 
 
Data Confidentiality  
All information and data sent to the Sponsor, Contract Research Organizations, or their designated 
agents concerning subjects or their participation in this study will be considered confidential and 
identifying information should be redacted.  All data used in the analysis and reporting of this 
evaluation will be used in a manner without identifiable reference to the subject.  The Principal 
Investigator consents to visits by the staff of the Sponsor and its authorized representatives and the 
U.S. Food and Drug Administration or any other local governmental body to review the study 
subjects’ medical records including any test or laboratory data. 
 
All information concerning the device, such as patent applications, formulas, manufacturing processes, 
scientific data, specific study designs, protocols, and formulation information supplied by the Sponsor 
and not previously published is considered confidential and will remain the sole property of the 
Sponsor.  The Principal Investigator agrees to use this information only in accomplishing the purposes 
of this study and will not use it for other purposes without the Sponsor’s written consent. 
 
Quality Assurance of the Data 
Subject case report forms will be reviewed against source documentation for completeness and 
accuracy.  If any discrepancies are noted, they will be resolved with the Investigator and/or designee.  
If the data are incomplete, attempts will be made to obtain the missing data.   
 
Monitoring Procedures 
The Alydia Health Vice President of Clinical Operations will have responsibility over the clinical 
study.  Monitors, the Independent Medical Monitor, and associated personnel will be recorded in the 
Trial Master File. 
The Sponsor is responsible for monitoring the study data to verify that the subject rights and well-
being are protected in accordance with applicable regulations, GCP, and Sponsor/CRO procedures.  
The Sponsor, or Sponsor designee, will perform clinical monitoring, including review of case report 
forms with verification to the source documentation.  Both remote and on-site monitoring may be 
conducted in this study.  The Investigator will allow direct access to all relevant subject files for the 
purpose of verifying entries made in the case report form and assist with the monitor’s activities as 
required.  Adequate time, office accommodations, and resources (e.g., copy machine, phone, and/or 
internet access) for monitoring visits should be made available to the monitor at clinical sites. 
                                                 
eligibility criteria. If the re-estimated pre-treatment EBL is >1800 ml, then it must be reported as a 
protocol deviation. 

           
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Monitors will contact the site prior to the start of the study to review with the site staff the protocol, 
study requirements, and their responsibilities to satisfy regulatory, ethical, and Sponsor’s requirements.   
The Sponsor/designee will periodically monitor the site activity to verify: 
• 
Data are authentic, accurate and complete. 
• 
Safety and rights of subjects are being protected. 
• 
Study is conducted in accordance with the currently approved protocol (including study 
treatment being used in accordance with the protocol). 
• 
Any other study agreements, GCP, and all applicable regulatory requirements are met. 
The Investigator and the head of the medical institution (where applicable) agree to allow the monitor 
direct access to all relevant documents. 
 
Publication Policy 
The Principal Investigator may not publish information obtained during this study prior to obtaining 
the review and approval of the Sponsor, which shall be in writing.  The Sponsor reserves the right to 
assert its proprietary interests regarding any confidential, technical or proprietary information that the 
Sponsor may have furnished the Principal Investigator in order to facilitate clinical studies under this 
agreement. 
9.0 
Statistical Analysis Plan 
 
Introduction 
This is a prospective, single-arm, literature-controlled, multi-center trial designed to assess the safety 
and effectiveness of the Jada System when treating primary PPH.  The study is designed to 
demonstrate that Jada provides safe and effective control or reduction of primary PPH. Safety will be 
evaluated by analyzing all adverse events for device relatedness, seriousness, severity, and whether or 
not they were anticipated. 
Up to 20 study sites will enroll a total of up to 107 subjects in the study to ensure that 96 subjects are 
available for the analysis of the primary effectiveness endpoint.  Qualified sites will be located in the 
U.S. and potentially O.U.S. as well.  Sites are expected to enroll a minimum of 5 subjects.  Site 
enrollment will be capped at 30% of the total expected enrollment, such that no site will enroll more 
than 32 subjects.  Also, no more than 50% of the study data will come from O.U.S. sites. 
 
Study Endpoint Analysis  
Reported Adverse Events 
Adverse events will be categorized as: 
• 
serious or non-serious,  
• 
severe, moderate or mild,  
• 
device-related, possibly device-related or non-device-related,  
• 
anticipated or unanticipated.   
 
The frequency of each event will be summarized according to the above categories.  Since some 
subjects may report the same event several times (e.g., headache), the first occurrence of the worst 
reported case of the event will be used for the purpose of analysis. 
 
Primary Effectiveness Endpoint – Treatment Success  

           
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Control of postpartum hemorrhage, defined as the avoidance of non-surgical, second line or surgical 
intervention to control uterine hemorrhage after the use of the Jada System per the Instructions for 
Use. 
 
Non-surgical, second line procedures include uterine balloon therapy, uterine packing, or uterine artery 
embolization.  Surgical intervention includes procedures such as uterine arterial ligation, uterine 
compression sutures or hysterectomy. 
 
Note: Continuation of the administration of uterotonics concomitant with and post Jada use is standard 
of care as long as such use does not exceed the maximum dose of the drug and does not constitute 
failure of the primary effectiveness endpoint. 
 
Study Success  
A thorough review of all known publications reporting on the use of the Bakri Balloon and other 
balloon tamponade methodologies to treat PPH was conducted.  A meta-analysis methodology was 
used to aggregate the studies and provide a numerical estimate of the overall Literature Treatment 
Success Rate. Based on a random effects model, the estimated pooled proportion of subjects who 
reached hemostasis (i.e., control of uterine hemorrhaging) following Bakri Balloon treatments was 
82.0% (95% CI: 73.4% to 89.2%). See the Clinical Evaluation Report (G150265, Attachment H, pages 
337-382). 
 
The primary effectiveness objective of this Pivotal Study is to show that the observed Study Treatment 
Success Rate is not worse that the rate reported in the literature.  The study is considered a success 
when the lower bound of the two-sided Exact Clopper-Pearson mid-p 95% Confidence Interval for the 
Study Treatment Success is greater than or equal to 73.4%.  
 
Secondary Endpoints 
1. Time to control hemorrhage, defined as the time from turning on the vacuum source until the time 
the first of any of the following occurs:  
• 
there is no blood being collected in the tubing or canister, or 
• 
the blood loss is observed as leveled off in the canister, or  
• 
blood loss at a rate of < 500 ml in 24 hours.  
2. Rate of surgical intervention required to control PPH after Jada use. 
3. Rate of non-surgical intervention required to control PPH after Jada use. 
4. Assessment of device usability as reported by the clinician using a dedicated data collection form. 
5. Rate of blood product transfusion required after Jada use, and number of transfusion units when 
administered. 
 
The secondary endpoints will be summarized, and confidence intervals will be provided to support 
interpretation of the results.  No specific hypothesis tests will be performed for the secondary 
endpoints.  
 
Analysis Cohorts 
Different groups of subjects, or Analysis Cohorts, will be identified depending on the type and extent 
of analysis being performed. 
 
Only subjects from study centers located within the United States and study centers located O.U.S. that 
have been enrolled under this version of the protocol (2.6) will be included in the analyses and data 
presentations defined in this protocol. 
 

           
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Screening Cohort 
All subjects who are consented and screened for the study will be included in the Screening Cohort.  
Subjects excluded during the procedure from receiving Jada treatment for non-device related reasons 
are included in this Cohort.  Only an accounting of the numbers of subjects screened in the study, plus 
the reasons given for subjects not enrolled in the study will be performed on this Cohort. 
 
Safety/ITT (Intent to Treat) Cohort 
All subjects in whom treatment was attempted with Jada (device inserted and vacuum turned on) are 
included in the Safety/ITT Cohort. 
 
Per-Protocol Cohort 
The Per-Protocol Cohort is defined as the group of subjects who are treated and complete treatment 
with the Jada System per the device’s Instructions for Use, and who complete their 6-week visit 
without any major protocol deviations. 
 
Cohort for Primary and Secondary Effectiveness Endpoints 
Analyses of all primary and secondary effectiveness endpoints will be repeated both for the Safety/ITT 
Cohort and for the Per-Protocol Cohort.  Study Success will be based on the Safety/ITT Cohort. 
 
Cohort for Safety Endpoints 
Analyses for all safety related endpoints will be performed using the Safety/ITT Cohort. 
 
Derived Data – Change-from-Baseline Parameters 
Within-subject change-from-baseline (pre-treatment baseline) values for a parameter are calculated as: 
Change-from-Baseline = Pre-Treatment value – Follow-Up value  
such that a positive value indicates a reduction from the pre-treatment value to the follow-up value, 
whereas a negative result indicates the opposite. 
 
Statistical Methods 
Categorical data will be summarized using frequency tables, presenting the subject counts and relative 
percentages. McNemar’s chi-square may be used to assess within-subject changes in a bivariate 
response variable. 
 
Continuous variables will be summarized by the mean, standard deviation, median, minimum and 
maximum.  Within-subject changes (Change-from-Baseline) will be analyzed parametrically using the 
Paired t-test if the differences are normally distributed, or non-parametrically using the Sign-Rank Test 
if the differences are not normally distributed. 
 
The SAS system or equivalent statistical package will be used to perform all analyses. Exact 
confidence intervals will be generated for estimates of proportions.  Asymptotic confidence intervals 
will be generated for estimates of means.  The p-values of all tests will be reported without any 
correction for the multiplicity of tests performed.   
 
Subgroup Analysis  
Analysis of the primary safety and effectiveness endpoints will be repeated for two subgroups of 
subjects: subjects with vaginal delivery and subjects with surgical delivery by Cesarean section. 
 Poolability 

           
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Data will be pooled from multiple study sites for this analysis.  The justification for pooling is made on 
a clinical basis3.  The basis for pooling comes from three critical factors: the study sites must implement 
one common protocol; the sponsor must provide monitoring of study site compliance; the study sites 
must use common data collection procedures. 
Poolability across study sites will be assessed by presenting Treatment Success Rates by site and 
analyzing site-to-site differences using the Chi-square Test.  Other methods for assessing site-to-site 
differences in Treatment Success Rates will be considered if the assumptions underlying the Chi-square 
Test are not met. Site-to-site differences will be assessed at a 0.15 level of significance.  A non-
significant site-to-site effect will support poolability of study sites.  Note that prior to assessing site-to-
site differences, sites with less than 5 subjects will be combined. To avoid the scenario that the data from 
the combined super-site dominate the trial conclusion, sites with less than 5 enrolled subjects be 
combined according to their geographical closeness, and once a super-site has five or more enrolled 
subjects, then the forming of this super-site will stop and the forming of a new super-site will start.  Site-
to-site differences of a quantitative nature, (e.g., all sites show the treatment to be beneficial, but perhaps 
to a different degree by study site) will not be considered to be an impediment to pooling.  Site-to-site 
differences qualitative in nature (e.g., the vast majority of sites show the treatment to be beneficial, but 
one or more sites show the treatment to be detrimental) will require extensive evaluation of the sites with 
contrary results to attempt to determine what factors at those sites led to the result. 
 Lost to Follow-up 
Data on subjects who are lost to follow-up or who withdraw from the study will be maintained and 
analyzed up to the point at which they discontinued.  The reason for withdrawal will be recorded if 
known.  Subjects who discontinue participation, for whatever reason, will remain in the study and be 
subject to follow-up in the same manner as those who complete the study except as noted above.  The 
only confirmed lost to follow-up subject will be a subject who dies or refuses to continue to participate 
in the study and thereby withdraws. 
 Dropout Mechanism and Analysis 
Subjects who are missing data necessary to assess Treatment Success will be considered a failure 
(Treatment Success = No) in the analysis of the primary effectiveness endpoint.  If the subject withdraws 
from the study prior to completing the assessment of Treatment Success, it will be considered missing 
data.  All other endpoints will be analyzed “as-is” without any special data imputation methods used to 
replace missing data. 
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3 Meinert, C. (1986). Clinical Trials: Design, Conduct, and Analysis.  Oxford University Press, New York. 

           
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guidance/prevention-and-management-postpartum-haemorrhage-green-top-52   
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garment for the treatment of obstetric hemorrhage in Egypt. Int J Gynaecol Obstet 2010 
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23. Franchini M, Franchi M, Bergamini V, et al. The use of recombinant activated FVII in postpartum 
hemorrhage. Clin Obstet Gynecol 2010 Mar;53(1):219-27. 

           
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24. Soltan MH, Faragallah MF, Mosabah MH, et al. External aortic compression device: the first aid 
for postpartum hemorrhage control. J Obstet Gynaecol Res 2009 Jun;35(3):453-8. 
25. Samartha Ram H, Shankar Ram HS, Sandhya Ram S, et al. Vacuum retraction for the management 
of atonic postpartum hemorrhage. ISOR J of Dental and Medical Sciences 2014 13(11):15-19 
26. Smets EMA, Garssen B, Bonke B, et al. The multidimensional Fatigue Inventory (MFI) 
psychometric qualities of an instrument to assess fatigue. J Psychosomatic Research 1995 
April;39(3):315-325. 
27. Schneider RA. Preliminary data on the Multidimensional Fatigue Inventory-20 from female 
caregivers of male hemodialysis patients. Pshchol Rep 2001 Jun;88(3 Pt 1):699-700. 
28. Bertelsen M, Broberg S, and Madsen E. Outcome of physiotherapy as part of a multidisciplinary 
rehabilitation in an unselected polio population with one-year follow-up: an uncontrolled study. J 
Rehabil Med 2009; 41: 85–87. 
29. Wong CJ, Goodridge D, Marciniuk D, et al. Fatigue in patients with COPD participating in a 
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