Marani Prenatal Connected Care (M•Care) Safety and Effectiveness Study
Conditions: Pregnancy
Sponsor: Marani Health

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
Protocol Number: MH-001   
Revision Number: G 
Page 1 of 46 
 
Confidential 
 
 
Refer to QMS Number: VAL-PRO-20-0004, Rev G 
DCR-00306, Effective – 14-Dec-2022 
 
STUDY PROTOCOL 
 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
 
Protocol Number: MH-001 
 
Revision: G 
14-Dec-2022 
 
NCT05294211 
  
 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
Protocol Number: MH-001   
Revision Number: G 
Page 2 of 46 
 
Confidential 
 
 
Refer to QMS Number: VAL-PRO-20-0004, Rev G 
DCR-00306, Effective – 14-Dec-2022 
PROTOCOL AGREEMENT FORM  
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
Revision G
 
I confirm that I have read the above-referenced protocol and understand its contents. The 
information it contains is consistent with the current risk-benefit evaluation of the investigational 
product.  
I agree to conduct the study according to this protocol and to comply with its requirements, subject 
to scientific, ethical, and safety considerations.  I will obtain the required Institutional Review Board 
(IRB) approvals prior to initiating the study and will abide by any additional requirements imposed 
by the IRB.  I will provide copies of this clinical study protocol and all pertinent information to the 
study personnel under my supervision and will discuss this material with them and ensure they are 
fully informed regarding the investigational product and the conduct of the study.  I agree to conduct 
the study in compliance with the Declaration of Helsinki, Clinical investigation of medical devices for 
human subjects – Good Clinical Practice (ISO 14155:2020 GCP), and applicable regulatory 
requirements.  
I understand that modifications to the study are acceptable only with mutually agreed upon protocol 
amendments. Should I decide to withdraw from participating in the study, I will immediately 
communicate such decision in writing to the Sponsor.  
 
 
 
_____________________________________________________________________________________ 
Clinical Site Name 
 
 
_______________________ 
_______________________ 
 
______________ 
Site Principal Investigator 
 
Site Principal Investigator 
 
Date 
(Print Name) 
(Signature) 
 
 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ................................................................................................................ 5 
1.1 
Synopsis .................................................................................................................................. 5 
1.2 
Schema ................................................................................................................................. 13 
2 
INTRODUCTION ........................................................................................................................... 14 
2.1 
Study Background ............................................................................................................... 14 
2.2 
Study Rationale .................................................................................................................... 15 
2.3 Benefit/risk assessment ................................................................................................................. 15 
3 
OBJECTIVES AND ENDPOINTS ............................................................................................... 16 
3.1 
Objective ............................................................................................................................... 16 
3.2 
Primary Performance Measures ........................................................................................ 16 
3.3 
Secondary Performance Measures .................................................................................. 17 
3.4 
Safety Endpoint Measures ................................................................................................. 17 
3.5 
Success Criteria Justification ............................................................................................. 17 
4 
STUDY DESIGN ............................................................................................................................ 19 
4.1 
Overall Design ...................................................................................................................... 19 
4.2 
End of Study Definition ....................................................................................................... 19 
5 
STUDY POPULATION ................................................................................................................. 20 
5.1 
Inclusion Criteria .................................................................................................................. 20 
5.2 
Exclusion Criteria ................................................................................................................. 20 
5.3 
Screen Failures .................................................................................................................... 21 
5.4 
Strategies for Recruitment .................................................................................................. 21 
6 
STUDY REGIMEN......................................................................................................................... 21 
6.1 
Study Administration ........................................................................................................... 21 
6.2 
Accountability ....................................................................................................................... 23 
6.2.1 
Acquisition and accountability .......................................................................... 23 
6.2.2 
Appearance and Labeling ................................................................................ 24 
7 
STUDY DISCONTINUATION AND SUBJECT DISCONTINUATION/WITHDRAWAL....... 24 
7.1 
Discontinuation of M•wrap Application/Subject Withdrawal .......................................... 24 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................................... 24 
8.1 
Efficacy Assessments ......................................................................................................... 24 
8.2 
Safety and Other Assessments ......................................................................................... 24 
8.3 
Adverse Events .................................................................................................................... 25 
8.3.1 
Adverse Events (AE) ......................................................................................... 25 
8.3.2 
Reporting of an Adverse Event ........................................................................ 25 
8.3.3 
Classification of an Adverse Event ................................................................. 25 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up .......... 26 
8.3.5 
Expedited Reporting Requirements  ............................................................... 27 
9 
STATISTICAL CONSIDERATIONS ........................................................................................... 27 
9.1 
Analysis Populations ........................................................................................................... 27 
9.2 
STUDY ENDPOINTS .......................................................................................................... 27 
9.2.1 
Primary Performance Measures ...................................................................... 27 
9.2.2 
Secondary Performance Measures ................................................................ 27 
9.2.3 
Safety Outcome Measures ............................................................................... 28 

 
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9.3 
Study Success Criteria ........................................................................................................ 28 
9.3.1 
Primary Performance Goals ............................................................................. 28 
9.3.2 
Secondary Performance Goal ......................................................................... 28 
9.4 
Statistical Analysis ............................................................................................................... 28 
9.4.1 
General Considerations  ................................................................................... 28 
9.4.2 
Subject Accountability, Demographic and Baseline Characteristics   ....... 29 
9.4.3 
Performance Measures Analyses  .................................................................. 29 
9.4.4 
Safety Measures AnalysIs  ............................................................................... 30 
9.4.5 
Additional Analyses and Considerations ........................................................ 31 
9.5 
Sample Size Justification .................................................................................................... 31 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............... 32 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ............................................ 32 
10.1.1 
Informed Consent Process ............................................................................... 32 
10.2 
Ethical Considerations ........................................................................................................ 33 
10.3 
Institutional Review Board (IRB) ....................................................................................... 33 
10.4 
Protocol Amendments ......................................................................................................... 34 
10.4.1 
Study Discontinuation and Closure ................................................................. 34 
10.4.2 
Confidentiality and Privacy ............................................................................... 34 
10.4.3 
Future Use of Data ............................................................................................ 35 
10.4.4 
Clinical Monitoring ............................................................................................. 35 
10.4.5 
Quality Assurance and Quality Control .......................................................... 35 
10.4.6 
Data Handling and Record Keeping ............................................................... 36 
10.4.7 
Protocol Deviations ............................................................................................ 36 
10.4.8 
Trial registration ................................................................................................. 37 
10.4.9 
Conflict of Interest Policy .................................................................................. 37 
10.5 
Abbreviations ........................................................................................................................ 37 
10.6 
Definitions ............................................................................................................................. 39 
10.7 
Protocol Amendment History ............................................................................................. 40 
11 
REFERENCES............................................................................................................................... 44 
12 
APPENDICES ................................................................................................................................ 46 
 
 
 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
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1 
 
PROTOCOL SUMMARY 
 
1.1 
SYNOPSIS  
 
PROTOCOL SYNOPSIS 
Study Title 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and Effectiveness 
Study (M•CARE SE Study) 
Procedure Name 
Antenatal Fetal Monitoring 
Sponsor 
Marani Health, Inc. 
Protocol Number 
MH-001 
Objective 
To demonstrate the safety and performance of the Marani Fetal 
Monitoring Telehealth System (M•care™ System) for use in antenatal 
monitoring of pregnant women ≥ 32 weeks’ gestation. The M•care System 
will be evaluated by comparing Fetal Heart Rate (FHR), Maternal Heart Rate 
(MHR) and Uterine Contractions (UC) to Doppler FHR, Pulse Oximeter MHR, 
and tocodynamometer (TOCO) UC, respectively, measured with an FDA 
cleared standard of care cardiotocography (CTG) device. 
Study Design 
This is a multi-center, single arm, prospective paired comparison trial to 
determine the equivalence of the Marani M•care System with an FDA 
cleared Doppler FHR, TOCO UC and Pulse Oximetry MHR standard of care 
CTG device. 
Duration 
The expected monitoring duration for each subject is a minimum of 60 
minutes and maximum of 120 minutes. 
Study Device 
Description 
Marani Health’s M•care System is a fetal heart rate (FHR), maternal heart 
rate (MHR), and uterine activity (UA) monitoring system intended for home 
use by a pregnant woman as prescribed by their healthcare provider. 
The M•care™ System is comprised of 3 components: 
(1) The M•wrap™, a wearable compression abdominal band with an 
integrated electronics hub, called the M•core™, mounted to the 
garment, that interfaces with 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
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(2) the removable Orbital Research SilverBump dry electrodes and 
(3) mobile and web-based software applications to securely transmit 
subject vital data to secure systems 
Owing to the unique placement of electrodes within the M•wrap, the 
functionality of the system is not dependent on fetal position. 
The M•care System is being developed in accordance with the requirements 
of FDA’s Quality System Regulation for Medical Devices, 21CFR Part 820, and 
ISO13485:2016 Medical Devices – Quality Management Systems – 
Requirements for Regulatory Purposes.  Both FDA and ISO 13485 mandate 
the use of Design Controls to ensure a formalized approach to development 
of medical devices. Marani Health has established Design Control procedures 
to ensure that a robust, and uniform product development methodology is 
being followed.  This methodology includes, but is not limited to, the 
following requirements: 
• 
Design and Development Plans are established, reviewed, updated, 
and approved. 
• 
Design Inputs are identified to ensure that design requirements are 
appropriate and address the intended use. 
• 
Design Outputs are defined to allow for adequate evaluation of 
conformance to design inputs. 
• 
Design Reviews are planned and conducted at appropriate stages 
during development. 
• 
Design Verification is performed to ensure the design output meets 
the design input requirements. 
• 
Design Validation is performed to confirm that devices conform to 
defined user needs and intended uses under actual or simulated use 
conditions. 
The output of these activities is maintained in a Design History File in Marani 
Health’s Quality Management System. 
Reference Device 
Philips Avalon FM20, Philips Avalon FM30, Philips Avalon FM40, or Philips 
Avalon FM50 (K140535) FDA cleared Doppler FHR, TOCO UC + Pulse 
Oximeter with a dedicated PC and cable connections. 
Indications for Use for the Philips Avalon FM20, FM30 FM40 or FM50 
reference device: 
Avalon Fetal/Maternal Monitor FM20: 
Indicated for use by trained health care professionals whenever there is a 
need for monitoring of the physiological parameters uterine activity, heart 
rate, oxygen saturation, noninvasive blood pressure, pulse rate and 
temperature of pregnant women and the fetal heart rates of single fetuses, 

 
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twins, and triplets in labor and delivery rooms, in antepartum testing areas, 
in private households and during transports in healthcare facilities. 
Avalon Fetal/Maternal Monitor FM30: 
Indicated for use by trained health care professionals whenever there is a 
need for monitoring of the physiological parameters uterine activity, heart 
rate, electrocardiography (ECG), oxygen saturation, noninvasive blood 
pressure, pulse rate and temperature of pregnant women and the fetal heart 
rates of single fetuses, twins, and triplets in labor and delivery rooms, in 
antepartum testing areas, in private households and during transports in 
healthcare facilities. 
Avalon Fetal/Maternal Monitor FM40: 
Indicated for use by trained health care professionals whenever there is a 
need for monitoring of the physiological parameters uterine activity, heart 
rate, oxygen saturation, noninvasive blood pressure, pulse rate and 
temperature of pregnant women and the fetal heart rates of single fetuses, 
twins, and triplets in labor and delivery rooms and in antepartum testing 
areas. 
Avalon Fetal/Maternal Monitor FM50: 
Indicated for use by trained health care professionals whenever there is a 
need for monitoring of the physiological parameters uterine activity, heart 
rate, electrocardiography (ECG), oxygen saturation, noninvasive blood 
pressure, pulse rate and temperature of pregnant women and the fetal heart 
rates of single fetuses, twins, and triplets in labor and delivery rooms and in 
antepartum testing areas. 
Number of Sites 
A minimum of 3 and up to 5 centers including: 
• 
Mayo Clinic (Rochester, MN) 
• 
NorthShore University HealthSystem (Evanston, IL) 
• 
St. Catherine’s University (St. Paul, MN) 
Countries 
United States 
Study Duration Per 
Subject 
Expected duration of the study is approximately 3 hours for each subject. 
This includes study recruitment and data collection. This is typically a single-
visit study; however, monitoring may occur during a separate visit after 
screening and consent have occurred. 
Total Study Duration 
The total expected study duration is 6 months. 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
Effectiveness Study (M•CARE SE Study) 
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Expected Study 
Enrollment 
Plan to recruit up to 130 subjects in total across all sites resulting in a 
minimum of 80 evaluable subjects to achieve performance endpoints.  No 
single site shall have greater than 50% of the patient recruitment population. 
Study Population 
 
Two study groups will be included in order to ensure collection of sufficient 
uterine contraction activity data. The study groups are as follows: 
• 
Antenatal – includes subjects evaluated per obstetric standard of care 
in the clinic/office environment and subjects completing research-
only visits in a non-clinic setting with oversight by a healthcare 
professional. Subjects with premature rupture of membrane (PROM) 
will also be included.  
• 
Enriched Hospital – includes subjects in early (latent) phase of labor 
with suspected or confirmed uterine contractions, and subjects who 
are being induced for labor. 
For all analyses, the combined Hospital and Antenatal groups will be 
considered the Primary Analysis Population. Additional supportive analyses 
will be conducted for each study group separately. 
An effort will be made to include subjects in each Body Mass Index (BMI) 
stratum. BMI measurements are pre-pregnancy. 
Hospital Group: 
• 
Subjects with a (BMI) ≤ 29 
• 
Subjects with a BMI > 29 but ≤ 35 
• 
Subjects with a BMI > 35 but ≤ 45 
Antenatal Group: 
• 
Subjects with a Body Mass Index (BMI) ≤ 29 
• 
Subjects with a BMI > 29 but ≤ 35 
• 
Subjects with a BMI > 35 but ≤ 45 
Inclusion Criteria 
Subjects eligible for this clinical study must fulfill all of the following criteria: 
1) 
Able to provide Informed Consent and follow study instructions 
2) 
18 years of age or older 
3) 
Pregnant subjects ≥ 32 weeks’ gestation 
4) 
Singleton pregnancy 
5) 
BMI ≥15, pre-pregnancy 
6) 
BMI ≤45, pre-pregnancy 
7) 
Belly circumference ≥80 cm and ≤ 135 cm 
NOTE: Subjects admitted for induction of labor and subjects being monitored 
for premature rupture of membranes (PROM) or other inpatient evaluations 
can be enrolled in the trial. 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
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Exclusion Criteria 
Subjects are not eligible if any of the following criteria are met: 
1) 
Known major fetal malformation or chromosome abnormality 
2) 
Abdominal medical skin conditions, including surgical incisions, open 
wounds with or without infections, edema, or irritation 
3) 
Subjects with implanted electronic devices (pacemakers, 
defibrillator, etc.) 
4) 
Involvement in another clinical trial currently or previously in this 
pregnancy that, in the investigator's opinion, would affect the 
conduct of this study. 
5) 
Medical or obstetric problem that in investigator's opinion would 
make the subject incapable of taking part in the study. 
6) 
In the investigator’s opinion, the subject is not likely to be available 
for the minimum 60 minutes of the monitoring session. 
7) 
History of skin allergies to cosmetics and lotions. 
8) 
Known allergies to silver, nylon, or polyester. 
Note: some people with sensitivity to silver jewelry are sensitive to 
the impurities in silver alloys and not to silver itself. 
Primary Performance 
Measures 
• 
Fetal Heart Rate (FHR) as measured by the M•care System versus 
standard of care CTG device. 
• 
Maternal Heart Rate (MHR) as measured by the M•care System 
versus the standard of care CTG Pulse Ox. 
Secondary 
Performance 
Measures 
The secondary performance measure is Uterine Contractions (UC) sensitivity 
as measured by the M•care System versus the standard of care CTG device.  
Hypothesis testing for UC sensitivity will only be conducted if the primary 
performance measures (i.e., equivalence in FHR and MHR) are met.  
Additional UC endpoints as measured by the M•care System versus standard 
of care CTG device include:  
• 
Positive predictive value (PPV) 
• 
False Positive Rate 
No hypothesis testing is planned for the PPV and false positive rate 
endpoints.  
Safety Outcome 
Measures 
• 
Incidence of device related and/or protocol procedure related 
adverse events related to the M•wrap study device 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
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Study Success Criteria 
Primary Performance Goals: 
• 
M•care FHR limit of agreement (LOA) within the performance goal of 
15 beats per minute (bpm) of FHR measured with CTG. 
• 
M•care MHR limit of agreement (LOA) within the performance goal 
of 10 beats per minute (bpm) of MHR measured with CTG. 
Secondary Performance Goal: 
• 
M•care UC detection sensitivity with a performance goal of greater 
than or equal to 80% agreement. 
Study Methodology 
Subjects will be assessed for study suitability based on the stated inclusion 
and exclusion criteria. Once informed consent is obtained, the study 
monitoring systems will be applied to the subject’s abdomen. 
Recording session: 
• 
Prior to deployment of the M•care system, subjects will be 
monitored with the external CTG device for fetal heart rate detection 
and the CTG pulse oximeter for maternal heart rate signal 
confirmation. 
• 
The M•wrap will be modified to allow positioning of the CTG 
transducers for simultaneous recording with both devices for FHR, 
MHR and UC (refer to Appendix 1). 
• 
The modified M•wrap will be secured to the subject’s abdomen and 
the subject will be monitored in stationary position for the duration 
of study recording session while following the M•wrap Instructions 
for Use. 
• 
Data is transmitted from the M•care system application to the 
Marani Cloud. There, the Marani proprietary signal processing is 
performed, and the data are analyzed to identify clean MHR, FHR 
and UC signals. Comprehensive analysis of the values will be 
performed offline. 
Each recording session will last for a minimum of 60 minutes and no longer 
than 120 minutes. Following the completion of the session, the study staff 
will remove the M•care monitoring system from the maternal abdomen and 
the study session will be concluded. 
The equivalence of the M•care System data will be compared to that of the 
simultaneously obtained reference device data. Complete monitoring strips 
will be obtained for each device and monitoring session to allow comparison 
for determination of equivalence. Comparison assessments between the 
M•care and CTG device will evaluate FHR, MHR and UC. Blinded review of UC 
data will be conducted by two physicians experienced in obstetrics; in the 
event of discordance, a third blinded reviewer will serve as an adjudicator. 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
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At all times, the M•care system shall be considered a research device. In the 
clinical setting (i.e., not a research-only visit), the M•care system is an 
adjunct to routine care and not a replacement for routine or urgent care 
needs. Only the data from the standard of care reference devices will be 
available to the clinical care team. Data recorded by the M•care system will 
not be accessible by study team members, thus clinical decisions for all 
subjects will solely be based on standard of care practices. 
Statistical 
Considerations 
Success Criteria: 
Study success will be based on the following two primary performance goals:  
Primary performance goal, FHR 
The primary performance goal will be met if the 95% confidence interval for 
the 95% limits of agreement (LOAs) between the M•care System and the 
standard of care reference device for the primary performance endpoint, 
FHR are within the performance goal interval of [-15, 15] bpm. 
Primary performance goal, MHR 
The primary performance goal will be met if the 95% confidence interval for 
the 95% limits of agreement (LOAs) between the M•care System and the 
standard of care reference device for the primary performance endpoint, 
MHR are within the performance goal interval of [-10, 10] bpm. 
Secondary performance goal, UC 
The performance goal for the secondary endpoint, UC, will be met if the 
lower bound of the 2-sided 95% confidence interval for sensitivity is greater 
than 80% for M•care as compared to standard of care reference device. 
Sample Size Justification: 
A sample size of N=80 evaluable subjects with an average of 60 minutes of 
comparative device data will provide adequate power to establish 
equivalence between M•care and standard of care in the primary 
performance measurements of FHR and MHR, and the secondary 
performance measurement of UC event sensitivity. It is anticipated that up to 
130 subjects from a minimum of 3 sites may be recruited to allow for 
inability of approximately 30% of subjects to complete the Monitoring 
Session per the study protocol. 
Background 
Mhajna et al reported the mean difference and (95% LOA) [SD] between 
INVU and standard of care reference CTG for FHR and MHR measurements as 
-0.30 bpm (-8.84, 8.24) [SD=4.36] and 0.28 (-5.30, 5.86) [SD=2.85], 
respectively.1 Furthermore, Hayes-Gill et al2 and Mhajna 20213,4 reported 
positive agreement (e.g., sensitivity) rates vs IUPC in uterine contraction 
events of 88%. 

 
MARANI PRENATAL CONNECTED CARE (M•care) Safety and 
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Power Considerations 
In this study, each recording session will last for a minimum of 60 minutes 
and no longer than 120 minutes yielding an assumed minimum of 30 
observations per subject for FHR and MHR, and an average of 3 UC events 
per subject. FHR and MHR are assumed to be normally distributed, with FHR 
mean (SD) of -0.3 (4.4), MHR mean (SD) of 0.3 (3).  UC sensitivity is assumed 
to be distributed binary, with UC sensitivity of 90%. For all measurements, 
the within subject correlation is assumed to be 0.5 and compound 
symmetric.  
Based on these assumptions and simulations with SAS 9.4 statistical software 
of MMRM and bootstrap resampling analyses, N=80 evaluable subjects will 
provide greater than 80% power (using either statistical method MMRM or 
bootstrap resampling) to establish equivalence between M•care and 
standard of care in each of the primary performance measurements of FHR 
and MHR and UC event sensitivity according to the success criteria and 
performance goals described above.  
 
 
 

 
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1.2 
SCHEMA 
The subject visit flow is described in Figure 1 below.   
 
Figure 1. Subject Visit Flow 
Once the Subject is present for data collection, the Setup and Monitoring Flow will proceed as shown in 
Figure 2.  Throughout this protocol, the groupings are referred to as either “Setup Flow” or “Monitoring 
Session.” 
 
Figure 2. Setup and Monitoring Flow 
Approach and 
discuss study with 
potential subject
Review consent and 
procedures, ensure 
understanding 
Complete consent 
process
Subject screening 
and demographics
Inclusion/exclusion 
met
Data and equipment 
CRF forms 
completed
Complete setup and 
monitoring (see flow 
below)
Confirm subject 
remuneration
Study Completion 
CRF

 
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2 
 
INTRODUCTION 
 
2.1 
STUDY BACKGROUND 
The U.S. has one of highest rates of maternal mortality in the industrialized world, putting the United 
States in the unenviable company of Afghanistan, Greece, and El Salvador.5 Each year in the US, 700 to 
900 women die from complications during pregnancy or childbirth. These numbers overshadow the more 
pervasive problem of severe maternal morbidity. Maternal health experts credit massive disparities in 
race, education, income, rural demographics, access to healthcare insurance and other socio-economic 
factors as prime reasons, accelerated by greater prevalence of C-sections, obesity, and chronic health 
issues including hypertension and diabetes. Pregnancy-related complications and premature births cost 
the US approximately $26B annually.  
In the US there are substantial differences in maternal morbidity rates seen across racial and ethnic lines: 
non-Hispanic black women, Hispanic, Asian/Pacific Islander and American Indian/Alaska Native women 
were also significantly more likely to have a severe morbidity related to childbirth than white women.6 
Non-Hispanic black women have had the fastest rate of increase in maternal deaths between 2007 and 
2014 and have maternal death rates up to 12 times higher in some cities than Non-Hispanic white 
women.7–9 According to a recent publication containing data from 2018 from the National Center for 
Health Statistics, wide racial gaps exist between non-Hispanic Black (37.1 deaths per 100,000 live births), 
non-Hispanic white (14.7) and Hispanic (11.8) women.10  
Monitoring systems used in labor and delivery are based on antiquated technology developed in the 
1960s. These systems are bulky, and many technologies are still hardwired, technologically demanding, 
and plagued with inconsistent, inaccurate data output. The Marani M•care system utilizes novel, non-
invasive sensors to leapfrog existing technology and provide inexpensive, easy-to-use garments that 
measure and record fetal electrocardiogram (fECG) along with other key biometrics.  
Current clinical assessment of potential fetal distress during pregnancies is done through infrequent 
monitoring of the vital signs of mother and unborn child. Existing technologies, including doppler 
ultrasound, are used in clinical settings.  
There are two types of monitoring-external and internal as standard of care:  
External monitoring is generally performed intermittently during pregnancy to monitor fetal heart status 
for brief periods or to perform a non-stress test (NST) and is often used during labor and delivery. Short 
term external monitoring can be done by listening to the fetal heartbeat with a stethoscope or a handheld 
doppler. External monitoring is also frequently performed using Cardiotocography (CTG). With CTG, a 
doppler ultrasound sensor measures FHR and a second sensor measures contractions.  

 
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A non-stress test (NST) measures FHR in response to either fetal movement or uterine contraction (UC). 
The goal of the NST is to determine how the heart of a fetus responds to the stimulus of a UC or to its own 
movements. In a normal (reactive) NST, a fetal heart rate will increase in response to a UC or to fetal 
movement.  At week 32 of pregnancy or later, if a baby's heartbeat accelerates to a certain level above 
the baseline twice or more for at least 15 seconds each within a 20-minute window, the results are 
considered reactive. If a baby's heartbeat does not meet the criteria described above, the results are 
considered nonreactive and further tests may be considered. 
External FHR monitoring is also done for a contraction stress test (CST), which records changes of the fetal 
heart rate during uterine contractions (UC). The aim of this test is to monitor the fetus to check for heart 
rate abnormalities in response to UC using cardiotocography. CST antenatal fetal surveillance technique 
may help predict the fetal capability to tolerate the stress of labor and vaginal delivery.  
Invasive internal monitoring using fetal scalp electrodes (FSE) and intrauterine pressure catheters (IUPC) 
are commonly used for intrapartum monitoring and management. These invasive technologies have 
known side effects including infection, particularly if the mother has an existing infection.  In addition, use 
of these technologies requires that the amniotic sac be ruptured, and the mother’s cervix be dilated to at 
least 2 cm. As such, these technologies are not generally available in the early stages of labor as standard 
of care.  
2.2 
STUDY RATIONALE 
Marani is developing a proprietary, wearable sensor platform technology to non-invasively acquire 
maternal and fetal biometric data, including fetal ECG (fECG). The Marani Health M•care System will allow 
clinicians to assess fetal heart rate non-invasively and wirelessly for prenatal monitoring.  
The Marani Health M•care System measures indicators of fetal and maternal wellbeing including fetal 
movements, maternal and fetal cardiovascular activity, and uterine contractions. The wearable system 
will simultaneously record both fetal and maternal parameters non-invasively. The Marani M•care 
product provides robust FHR, MHR and UC measurements compared to the standard of care CTG 
monitoring devices. 
2.3 BENEFIT/RISK ASSESSMENT 
This is a minimal risk study.  The subjects in this study are not expected to be at any higher or additional 
risks than those who undergo cardiotocography (CTG) monitoring in clinic or hospital settings. There is 
minimal risk with CTG monitoring.   
The M•wrap device employs electrocardiograph electrode sensors that are Food and Drug Administration 
(FDA) cleared. An electrocardiograph electrode is an electrode applied directly to the subject’s skin to 
passively acquire and transmit the electrical signal at the body surface to a processor that produces an 
electrocardiogram (ECG) or vectorcardiogram. An electrocardiograph electrode is not intended to deliver 

 
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therapy to the subject, and information collected from the subject using the M•wrap will not be used to 
provide any treatment or treatment recommendations during the study. There is no personal benefit to 
the subject for taking part in this study. Subject benefit is limited to the understanding that they are 
contributing to research on a new device that may benefit others in the future.  
The M•wrap is worn like tight-fitting compression clothing. Some people may view this as mildly 
uncomfortable.  In addition, pressure artifacts on the abdomen or back are expected.  Anticipated risks of 
the M•wrap system include but are not limited to known events associated with the use of ECG electrode 
systems and compression garments.   
• 
Redness (erythema) 
• 
Swelling (edema) 
• 
Irritation  
• 
Sensitization  
Skin irritation will be carefully monitored before, during, and after the study session.  Subjects will be 
immediately evaluated by the site investigator for any relevant unexpected skin irritation. Marani has 
designed the M•wrap to meet all applicable performance standards.   
Privacy Protection: Acquired data from this study will be stored on HIPAA-compliant, encrypted servers. 
Only investigators, engineers, statisticians, and other study personnel involved in data recording and 
interpretation will be allowed access to these data.  
3 
OBJECTIVES AND ENDPOINTS 
 
3.1 
OBJECTIVE 
The objective of this study is to demonstrate the safety and performance of the Marani Fetal 
Monitoring Telehealth System (M•care™ System) for use in antenatal monitoring of pregnant women ≥ 
32 weeks’ gestation. The M•care System will be evaluated by comparing Fetal Heart Rate (FHR), 
Maternal Heart Rate (MHR) and Uterine Contractions (UC) to Doppler FHR, Pulse Oximeter MHR, and 
tocodynamometer (TOCO) UC, respectively, measured with an FDA cleared standard of care 
cardiotocography (CTG) device. 
3.2 
PRIMARY PERFORMANCE MEASURES  
1) M•wrap FHR limit of agreement (LOA) within the performance goal of 15 beats per minute (bpm) 
of FHR measured with CTG 
2) M•care MHR limit of agreement (LOA) within the performance goal of 10 beats per minute (bpm) 
of MHR measured with CTG 

 
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3.3 
SECONDARY PERFORMANCE MEASURES  
The secondary performance measure is Uterine Contractions (UC) sensitivity as measured by the M•care 
System versus the standard of care CTG device, with a performance goal of greater than or equal to 80% 
agreement. Sensitivity is defined as the proportion of UC events identified by standard of care that are 
simultaneously (e.g., within 30 seconds) identified by the M•care System.  
Hypothesis testing for UC sensitivity will only be conducted if the primary performance measures (i.e., 
equivalence in FHR and MHR) are met.  
Additional UC endpoints as measured by the M•care System verses standard of care CTG device include: 
1) Positive predictive value (PPV) defined as the proportion of UC events identified by both the 
M•care System and standard of care out of those that are identified by the M•care System 
2) False Positive Rate defined as the proportion of UC events identified by the M•care System that 
are not identified by the standard of care 
No hypothesis testing is planned for the PPV and false positive rate endpoints.  
3.4 
SAFETY ENDPOINT MEASURES  
Incidence of device related and/or protocol procedure related adverse events (AEs) related to the study 
device, The Marani Health M•care System, in pregnant women with a singleton pregnancy ≥32 gestational 
weeks. Due to minimal risk, we do not expect any related serious events (see safety in section 8).  
3.5 
SUCCESS CRITERIA JUSTIFICATION  
Fetal Heart Rate (FHR) 
The primary performance endpoint is M•care FHR limit of agreement (LOA) within 15 beats per minute 
(bpm) of FHR measured with cardiotocography. This 15 bpm LOA is a clinically acceptable range to 
recognize common clinical phenomena including bradycardia, tachycardia, accelerations, and 
decelerations.7 Most FHR clinical phenomena are defined as an increase or decrease of 15 bpm from 
baseline, which could be detected given a 15-bpm limit of agreement. Clinical practice guidelines state 
that moderate FHR variability, between 5 and 25 bpm, is considered normal.11 Baseline HR variability can 
range from 3-12 bpm as measured with standard CTG, and which increases with gestational age.7,12 
Moreover, FHR calculations derived from CTG have previously been shown to have a high degree of 
inaccuracy when compared with those derived from fetal ECG-based measurements.7 Thus, given the 
known limitations of CTG, some of variability quantified by the limits of agreement in this study may be 
due to error in CTG measurements and not M•wrap measurements.  
In a study reported by Cohen, et al, the limits of agreement for both FHR and MHR with FSE, abdominal 
fetal ECG and ultrasound were clinically evaluated.13 In this study, the abdominal fetal ECG limits of 

 
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agreement (± 1.96 SD) for fECG to FSE was 8.40; −8.72 and for the Doppler ultrasound technique the bias 
is significantly greater, −2.87, with limits of agreement of (22.65, −28.39)7 indicating an even wider interval 
may be considered clinically insignificant. The FHR performance goal interval of [-15, 15] bpm is based on 
the clinically significant margin for differences in FHR that have been variously reported in the literature 
as: >15bpm (e.g., large acceleration)14, and >25bpm (e.g., marked baseline variability).15 
The mean difference (bias) between FHR measurements with fECG and Doppler methods has been 
reported as 0.74 bpm with 95% LOA of +/- 12 bpm (e.g., SD= 6.1 bpm) by Reinhard et al14, and -0.3 bpm 
with 95% LOA of (-8.84, 8.24) (e.g., SD=4.36) by Mhajna et al.1  The Monica Health Novii wireless patch 
system Instructions for Use (107-PT-005-EN rev P) indicates that when comparing the Monica Novii 
System and the predicate Monica AN24 System, the 95% LOA was -13.7BPM to 14.1 BPM. 
Maternal Heart Rate (MHR) 
The primary performance endpoint is M•care MHR limit of agreement within 10 beats per minute (bpm) 
of MHR measured with Pulse Oximetry MHR with the CTG.   It has been shown that a woman’s heart rate 
increases by an average 10 to 20 bpm during pregnancy.16 The mean heart rate at 34-42 weeks’ gestation 
was reported by Van Oppen et. Al as 92 ± 1.17  Sherman, et. al showed that heart rate variability is 15.8 ± 
1.8 during the latent phase and 12.7 ± 1.1 during the active phase of the first stages of labor.18 Other 
clinical studies have chosen an increase or decrease in heart rate of ≥10 beats per minute (bpm) at the 
peak of a contraction as compared to 10 seconds before the contraction to be regarded as either an 
acceleration or deceleration.19 As such, these reports support that a 10 bpm LOA is a clinically acceptable 
range to recognize common clinical phenomena including accelerations and decelerations. Additional 
considerations for tachycardia and bradycardia have been considered.  Odendaal et al. reported that 
tachycardia is defined as a “rate of at least 100 beats per minute under resting conditions” while the 
definition of bradycardia in pregnancy “has not been standardized.”20  
Uterine Contractions 
Uterine contractions are identified based on the tracings output by the relevant device; knowledgeable 
readers interpret the tracings to identify the contractions. The outcomes are binary: either the event 
happened, or it did not. To evaluate the performance of this binary outcome, our success criterion is to 
obtain results consistent with cleared devices with similar technologies such as the Monica AN24 per 
K101801 510(k) Summary, Monica Novii Instructions for Use (107-PT-005-EN rev P), and TOCO13 in 
general.   

 
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4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
Hypothesis: We hypothesize that non-invasive electrical recordings will permit acquisition of the fetal 
ECG, maternal ECG and uterine contractions (UC) with proper signal processing and will ultimately support 
the development of an abdominal fetal monitor that is wireless and unobtrusive. This will be accomplished 
with the Marani M•wrap wearable garment. 
This study is a prospective paired comparison, multi-site trial intended to establish the equivalence of the 
Marani M•care System with FDA-cleared Doppler FHR, TOCO UC and pulse Ox MHR reference. Subjects 
who are admitted to triage for potential labor or other inpatient evaluations including but not limited to 
evaluation for PROM, who are attending in-clinic appointments for Non-Stress Tests (NST), Contraction 
Stress Test (CST), or at the convenience of the subject will be monitored with both devices simultaneously 
for FHR, UC, and MHR. Only the data from the CTG device, the standard of care, will be available to the 
clinical team in a clinical setting. CTG information will not be interpreted in a non-clinic research visit 
setting. The M•care System data will be compared to that of the simultaneously obtained standard of 
care CTG data to determine equivalence after the monitoring is completed. No interim analysis is planned. 
4.2 
END OF STUDY DEFINITION 
Subjects will complete this study Setup and Monitoring sessions in a single visit.  Consenting and Screening 
may occur at a different time prior to Setup. Each individual subject study will be considered complete 
when all the following conditions have been met:  
• 
Consenting process has been completed   
• 
M•wrap monitoring is complete for that subject  
• 
Transmission of subject data has been confirmed by Marani, and  
• 
All study CRFs are finished. 
The overall study will be considered complete when all the following conditions have been met:  
• 
All subjects have completed their study visits as described above  
• 
Data queries have been adjudicated  
• 
Database is closed, and  
• 
All sites have had their closeout monitoring visits and received their closeout confirmation letter. 

 
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5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
Subjects eligible for this clinical study must fulfill all the following criteria: 
1) Able to provide Informed Consent and follow study instructions 
2) 18 years of age or older 
3) Pregnant subjects ≥ 32 weeks’ gestation  
4) Singleton pregnancy 
5) BMI ≥15, pre-pregnancy 
6) BMI ≤45, pre-pregnancy   
7) Belly circumference ≥80 cm and ≤ 135 cm 
NOTE: Subjects admitted for induction of labor and subjects being monitored for premature rupture of 
membranes (PROM) or other inpatient evaluations can be enrolled in the trial. 
5.2 
EXCLUSION CRITERIA 
Subjects are not eligible if any of the following criterion are met: 
1) Known major fetal malformation or chromosome abnormality 
2) Abdominal medical skin conditions, including surgical incisions, open wounds with or 
without infections, edema, or irritation 
3) Subjects with implanted electronic devices (pacemakers, defibrillator, etc.) 
4) Involvement in another clinical trial currently or previously in this pregnancy that, in the 
investigator's opinion, would affect the conduct of this study. 
5) Medical or obstetric problem that in investigator's opinion would make the subject 
incapable of taking part in the study. 
6) In the investigator’s opinion, the subject is not likely to be available for the minimum 60 
minutes of the monitoring session. 
7) History of skin allergies to cosmetics and lotions. 
8) Known allergies to silver, nylon, or polyester.  
Note: some people with sensitivity to silver jewelry are sensitive to the impurities in silver 
alloys and not to silver itself.  

 
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5.3 
SCREEN FAILURES 
Consented screen failures are defined as subjects who consent to participate in the clinical trial but are 
not entered into the study due to unmet inclusion or exclusion criteria. A screen failure log will be 
maintained at each site.  
5.4 
STRATEGIES FOR RECRUITMENT 
Recruitment will include pregnant women (≥32 weeks) who are coming to clinic for routine antenatal 
visits, scheduled research visits, or who are presenting for scheduled induction of labor, admitted for 
premature rupture of membranes (PROM) or other inpatient evaluations, in observation in labor triage. 
Visits will be scheduled at the convenience of the mother.  
The study will enroll a minimum of 80 evaluable subjects. Two study groups will be included in order to 
ensure collection of sufficient uterine contraction activity data. The study groups are as follows: 
• 
Antenatal – includes subjects evaluated per obstetric standard of care in the clinic/office 
environment and subjects completing research-only visits in a non-clinic setting with oversight 
by a healthcare professional. Subjects with premature rupture of membrane (PROM) will also be 
included.  
• 
Enriched Hospital – includes subjects in early (latent) phase of labor with suspected or 
confirmed uterine contractions, subjects who are being induced for labor. 
6 
STUDY REGIMEN 
 
6.1 
STUDY ADMINISTRATION 
The group of subjects enrolled into the study may include subjects scheduled for routine antenatal visits; 
participation in the study may be offered while in the office for their scheduled visit. Other eligible subjects 
may be recruited from the general population for a scheduled research visit in a non-clinical setting. Each 
subject may identify a time that works best for them. During the visit (subjects must be 32 weeks or 
greater), fECG, mECG signals and UC will be recorded. The aim is to record signals for up to 120 min. The 
definition of success is: (1) capture of signals with CTG and (2) validation that the M•wrap is capturing 
signals. 
The sequential order for recording, based on our estimation of the likelihood of success, is as follows: 
1. Apply the CTG doppler transducer and confirm the CTG doppler transducer is operating normally.  
Remove the doppler transducer and put on M•wrap. 
2. Utilize M•wrap + CTG (FHR, MHR, and UC) to collect data.  

 
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For purposes of recording signals, data will be collected from the subject simultaneously using both the 
M•wrap and CTG.  Refer to Section 1.2 for the expected step-by-step Study Schema. The FHR will be 
located with the doppler transducer on the CTG.  Once a strong FHR is located, prepare for and conduct 
placement of the appropriately sized M•wrap placement per the current Instructions for Use (IFU) 
Manual. With guidance from Marani, holes/openings will be created in the wrap fabric to allow for 
placement of the CTG transducers such that both devices can be used simultaneously.  See Figure 3 for an 
example of wrap placement and use of the wrap with CTG transducers. Appendix 1 describes M•wrap 
configurations for concurrent CTG use in more detail. The black compression band will be placed over the 
M•wrap and the CTG transducers throughout simultaneous data collection (see Figure 4). Marani 
personnel will be present to perform necessary device modifications to allow for CTG placement and to 
initiate data collection from the M•care Mobile Application.  
Based on the design of the M•care Mobile Application, each 60-to-120-minute Monitoring Session may 
include up to four data collection initiations from the M•care Mobile Application.  The mother may get 
up and walk around between data collection sessions.  
 
Figure 3. M•wrap with Example CTG Placement 
 
Figure 4. Black Compression Band over M•wrap and 
CTG Transducers 
Uterine contractions will be recorded using the standard external acquisition tocodynamometer system 
within the CTG, and the information synchronized to the recorded biopotential signals.  These signals 
will be collected over a 60-120 min period.   
Figure 5 depicts the connectivity of the Marani M•care System. The M•wrap signal will stream via 
Bluetooth through the M•core to a Marani-provided mobile phone containing either Android or iOS 
operating system and then to a secure Marani server (utilizing Amazon Web Services).  The CTG signals 
labeled only with Subject ID will be extracted from a MIB / RS232 port on the CTG machine and captured 
on a Marani-provided laptop for analysis and comparison to the M•wrap data. A Medicollector Cable CBL-
5010 will be used to connect the CTG to the Marani-provided laptop. For the purpose of this study, the 

 
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subject-facing mobile application will be controlled by Marani.  Site specific procedures will be followed 
for information security.  
 
Figure 5. Marani M•care System 
Study subjects may be asked to be photographed to demonstrate where the electrodes are meeting the 
subject’s abdomen, and possibly for publication. Photographs will only include abdominal pictures of the 
M•wrap; no identifying photos of faces will be included. 
Study garments and cores will be reused across subjects. Cleaning procedures to allow for reuse of 
garments are in accordance with FDA and CDC guidelines for non-critical subject care items. Applicable 
references include FDA's 2015 Guidance "Reprocessing Medical Device in Health Care Settings; Validation 
Methods and Labeling" and CDC’s 2008 Guideline document, "Guideline for Disinfection and Sterilization 
in Healthcare Facilities." 
6.2 
ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
An adequate number of M•wrap and M•core devices will be supplied to each study site prior to initiating 
the study and may be resupplied as needed. Each shipment of device supplies for the study will contain a 
shipment form to assist in maintaining current and accurate inventory records. When a device shipment 
is received, the investigator/coordinator will acknowledge receipt.  
Accountability records will be maintained at the site at all times. The identification number of the subject, 
the date, lot number, expiration date of the M•wrap dispensed, and the date and quantity of devices 
returned will be recorded. The devices will be noted on the appropriate inventory forms. Per Marani 
Health or Marani Health designee visit at the site, accountability of the returned devices should be 
performed and recorded. 
Upon conclusion of the study, all devices must be returned to the sponsor or the sponsor’s designee. 
Ancillary supplies (i.e., CTG bands, isopropyl alcohol, mild detergent, ultrasound gel for CTG transducers) 
may not need to be returned.  

 
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6.2.2 APPEARANCE AND LABELING 
The devices provided for this study will be labeled as investigational use only. Unique identifiers will be 
recorded to enable tracking of necessary device elements.  Software versions used in the clinical study 
will be recorded. 
7 
STUDY DISCONTINUATION AND SUBJECT DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF M•WRAP APPLICATION/SUBJECT WITHDRAWAL 
Subjects may withdraw from the study at any time. In the event that a subject experiences any adverse 
events, the protocol may be stopped, and the investigators will analyze the root cause. In addition, fetal 
wellbeing will be monitored and, if there are any effects considered to be the result of the study, the study 
may be stopped and there will be routine management of any subject if being seen in a clinical setting. If 
the subject is being seen in a non-clinic research setting, no CTG data will be interpreted and any adverse 
events requiring medical attention will be referred to the subject's physician. All adverse events will be 
followed with relevant records requested until resolution whenever possible. Each site investigator in a 
clinical setting will be responsible for determining appropriate clinical care. Site clinical staff may also 
make the decision to withdraw a subject for any other reason. 
The reason for withdrawal/discontinuation should be recorded on the appropriate case report form (CRF). 
Data collected up to the point of withdrawal may be used.  
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
EFFICACY ASSESSMENTS  
In order to assess efficacy, data will be collected simultaneously with both the M•wrap and CTG; this 
allows for a direct comparison of data obtained. CTG is considered standard of care and only that 
information will be used for clinical interpretation if the research is carried out in a clinical setting. The 
M•wrap data will not be shared with the practitioner or the subject and will not be used for any clinical 
interpretation or interventions.  In the event the M•wrap location and position prevents CTG data 
acquisition necessary for care, the M•wrap will be removed, replaced, or repositioned.  The study session 
will be stopped if standard of care cannot be achieved with the M•wrap in place.  
8.2 
SAFETY AND OTHER ASSESSMENTS 
During the time any subject is wearing the M•wrap, safety will be monitored. In the clinical setting, a 
qualified site staff member designated as having appropriate clinical expertise will make determinations 
regarding appropriate clinical care and care will be provided for any adverse events. If adverse events 
occur in the non-clinical setting, subjects will be referred to a clinician for treatment as needed.  

 
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In the clinical setting, monitoring for fetal wellbeing with standard of care shall be continued. If the subject 
is being seen in a research visit setting, no interpretations will be made from CTG or the M•wrap.  
8.3 
ADVERSE EVENTS 
 
8.3.1 ADVERSE EVENTS (AE) 
Refer to section 10.6 for a list of adverse event terms and definitions.  
Adverse events (AEs) will be monitored throughout the study period. All adverse events that occur during 
the time a subject is wearing the M•wrap will be collected and reported to Marani according to section 
8.3.2. Potential AEs for this study are listed in the ‘Benefit/Risk Assessment’ in Section 2.3. Events or 
complications unrelated to the M•wrap system will not be collected after removal of the M•wrap device. 
Since the study procedures are not greater than minimal risk, Serious Adverse Events (SAEs) are not 
expected. If any problems related to subjects do occur, these will be reported to the Institutional Review 
Board (IRB) in accordance with the local institution’s applicable policies and procedures. 
8.3.2 REPORTING OF AN ADVERSE EVENT 
All AEs and device deficiencies should be reported to Marani Health on the appropriate CRF within 24 
hours of awareness. Marani Health will be responsible for device servicing and replacements. 
AEs that are not serious but that are notable and could involve risks to subjects will be summarized in 
narrative or other format and submitted to the IRB per local IRB reporting requirements.   
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
Adverse events will be classified by seriousness, severity, and relationship to study device and protocol 
procedures. Marani Health will be responsible for device servicing and replacements. 
For adverse events, the following guidelines will be used to describe severity.  
• 
Mild – Events require minimal or no treatment and do not interfere with the subject’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a subject’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating.  Of 
note, the term “severe” does not necessarily equate to “serious”. 

 
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8.3.3.1 RELATIONSHIP TO STUDY APPLICATION 
All adverse events will have their relationship to study application and protocol procedures assessed by 
the study staff who examines and evaluates the subject based on temporal relationship. The degree of 
certainty about causality will be graded using the categories below.  
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study application administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study application (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study application, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the study application). However, other 
factors may have contributed to the event (e.g., the subject’s clinical condition, other concomitant 
events). Although an AE may rate only as “possibly related” soon after discovery, it can be flagged 
as requiring more information and later be upgraded to “probably related” or “definitely related”, 
as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study application administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the study 
application) and in which other drugs or chemicals or underlying disease provides plausible 
explanations (e.g., the subject’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study application administration, and/or 
evidence exists indicating that the event is definitely related to another etiology. An alternative, 
definitive etiology must be documented by the study staff. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE may come to the attention of study personnel during study visits and interviews 
of a study subject presenting for medical care, or upon review by a study monitor. 

 
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All AEs will be captured on the appropriate CRF. Information to be collected includes event description, 
time of onset, study staff’s assessment of severity, relationship to study product and protocol procedures, 
and time of resolution/stabilization of the event. All AEs will be followed to adequate resolution. 
8.3.5  EXPEDITED REPORTING REQUIREMENTS  
An investigator shall submit to the sponsor and to the reviewing IRB a written report of any unanticipated 
adverse device effect (UADE) occurring during an investigation according to the IRB’s applicable policies 
and procedures, but in no event later than 10 working days after the investigator first learns of the effect 
(21 CFR 812.150(a)(1)). 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
ANALYSIS POPULATIONS 
For all analysis populations the Hospital and Antenatal groups will be combined. Additional supportive 
analyses will be conducted for each study group separately.  
The safety analyses will be conducted for the Safety Population defined as the population of subjects who 
enter the setup process (see Section 1.2, Schema) regardless of evaluability for performance measures. 
The Performance Evaluable Population will be the primary analysis population for performance 
measures and will be defined as the population of subjects who: 
• 
Enter the monitoring phase per Section 1.2, Schema; 
• 
Have at least 1 minute of concurrent data with both devices; and  
• 
Do not have any major protocol violations. 
9.2 
STUDY ENDPOINTS 
9.2.1 PRIMARY PERFORMANCE MEASURES 
• 
Fetal Heart Rate (FHR) as measured by the M•care System versus standard of care CTG device.  
• 
Maternal Heart Rate (MHR) as measured by the M•care System versus the standard of care CTG Pulse 
Ox.  
9.2.2 SECONDARY PERFORMANCE MEASURES 
The secondary performance measure is Uterine Contractions (UC) sensitivity as measured by the M•care 
System versus the standard of care CTG device. Sensitivity is defined as the proportion of UC events 
identified by standard of care that are simultaneously (e.g., within 30 seconds) identified by the M•care 
System. 

 
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Hypothesis testing for UC sensitivity will only be conducted if the primary performance measures (i.e., 
equivalence in FHR and MHR) are met.  
Additional UC endpoints as measured by the M•care System versus standard of care CTG device, include: 
• 
Positive predictive value (PPV) defined as the proportion of UC events identified by both the M•care 
System and standard of care out of those that are identified by the M•care System.  
• 
False Positive Rate defined as the proportion of UC events identified by the M•care System that are 
not identified by the standard of care. 
No hypothesis is planned for the PPV and false positive rate endpoints. 
9.2.3 SAFETY OUTCOME MEASURES 
Incidence of device related and/or protocol procedure related adverse events (AEs) related to the M•wrap 
study device. 
9.3 
STUDY SUCCESS CRITERIA 
9.3.1 PRIMARY PERFORMANCE GOALS 
Study success will be based on the following: 
• 
M•care System limit of agreement (LOA) as compared with CTG within the performance goal of 
15 beats per minute (bpm) for FHR.  
• 
M•care System limit of agreement (LOA) as compared with CTG within the performance goal of 
10 beats per minute (bpm) for MHR.  
9.3.2 SECONDARY PERFORMANCE GOAL 
• 
M•care System UC detection sensitivity with a performance goal of greater than or equal to 80% 
agreement with CTG. 
9.4 
STATISTICAL ANALYSIS 
9.4.1 GENERAL CONSIDERATIONS  
Each recording session will last for a minimum of 60 minutes and no longer than 120 minutes with multiple 
observations per subject for FHR and MHR and UC events. For analysis of UC events, blinded review will 
be conducted by two physicians experienced in obstetrics. In the event of discordance, a third blinded 
reviewer will serve as an adjudicator.  

 
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Descriptive statistics will include n, mean, median, standard deviation, minimum and maximum for 
continuous data and n and percentages for categorical data. To account for the correlation among 
multiple measurements within subjects, MMRM (mixed-effect model repeated measures) statistical 
methods will be utilized for the primary analyses, with bootstrap resampling methods conducted as a 
supportive analysis. Unless otherwise specified all statistical tests will be conducted at a 2-sided alpha of 
5%. 
9.4.2 SUBJECT ACCOUNTABILITY, DEMOGRAPHIC AND BASELINE CHARACTERISTICS   
For each analysis population, the number of subjects will be summarized for each accountability status 
(e.g., consented, screen failed, enrolled, completed study, or withdrawn). Subjects excluded from an 
analysis population will be provided in a listing including reason for exclusion (e.g., non-evaluable for 
performance measures, major protocol deviation, etc.). 
For this study, enrollment is defined as subjects who enter the Setup phase per Section 1.2, Schema. 
Subjects who do not meet these minimum criteria will not be considered enrolled and will not be included 
in any analysis of performance for safety measures.  
Demographic characteristics (age, sex, race, ethnicity, height, weight, pre pregnancy BMI) will be 
summarized using descriptive statistics for each analysis population.  
Baseline obstetrical characteristics will be summarized using descriptive statistics for each analysis 
population, including obstetrical history, appointment or admission type, and belly circumference.  
9.4.3 PERFORMANCE MEASURES ANALYSES  
Primary Performance Measures Analysis 
A comparison between M•care measurement of FHR vs the standard of care reference measurements 
will be made using methods described below to test the following equivalence hypothesis corresponding 
to the Success Criteria defined in Section 3.5 of this protocol: 
H0: Upper 95% LOA > 15 bpm or Lower 95% LOA < -15 bpm      vs  
 
H1: -15 bpm ≤ Lower 95% LOA and Upper 95% LOA ≤ 15 bpm 
A Bland-Altman plot of the mean versus the difference will be presented, and the 95% limits of agreement 
(LOA) calculated together with respective 95% confidence intervals, which will be compared to the 
equivalence threshold (e.g., performance goal). Both MMRM analysis (primary) as well as bootstrap 
resampling techniques (supportive) will be conducted to account for the correlation among repeated FHR 
measurements within subjects. For the MMRM analysis, the mean difference (bias) and its standard 
deviation will be estimated from the intercept of the model, assuming a compound symmetric correlation 

 
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structure, with the 95% LOA and corresponding 95% confidence intervals calculated as defined by Lu 
2016.21 MMRM analysis provides for valid inference in the presence of data that is missing at random.  
In addition, a Deming regression model will be fitted to the FHR values obtained from both devices; the 
slope (β1) and intercept β0) together with respective 95% confidence intervals will be presented. The 
confidence intervals of the regression parameters will be calculated with bootstrap resampling 
methodology, to accommodate repeated measurement within subjects. The results will be presented 
graphically via scatter plot with the line of slope 1 and intercept 0 superimposed. 
A comparison between M•care measurement of MHR vs the standard of care reference measurements 
will be made using the methods described above to test the following equivalence hypothesis Success 
Criteria defined in Section 3.5 of this protocol: 
H0: Upper 95% LOA > 10 bpm or Lower 95% LOA < -10 bpm      vs  
 
H1: -10 bpm ≤ Lower 95% LOA and Upper 95% LOA ≤ 10 bpm 
Secondary Performance Measures Analysis 
A comparison of sensitivity in UC events detected with M•care measurement vs the standard of care will 
be made using methods described below to test the following hypothesis: 
H0: Sensitivity < 80%     vs    H1: Sensitivity ≥ 80% 
To compare sensitivity (percent positive agreement) in UC events between M•care and standard of care, 
both MMRM analysis for binary data (primary) and bootstrap resampling techniques (supportive) will be 
used to account for the correlation among repeated UC measurements within subjects. For the MMRM 
model, the sensitivity will be estimated from the intercept of the model, presented with corresponding 2-
sided 95% confidence interval (e.g., corresponding to a 1-sided alpha 2.5%). 
Estimates of false positive rate and PPV in UC events detected with M•care measurement vs the standard 
of care will be made using both MMRM analysis for binary data (primary) and bootstrap resampling 
techniques (supportive), to account for the correlation among repeated UC measurements within 
subjects. For the MMRM model, estimates will be from the intercept of the model, presented with 
corresponding 2-sided 95% confidence interval.  
Primary and secondary performance measures will also be summarized using descriptive statistics for FHR 
and MHR, and using a 2x2 cross tabulation table for UC events.  
9.4.4 SAFETY MEASURES ANALYSIS  
The incidence and overall counts and classifications of adverse events that are related to the M•wrap 
study device and/or protocol procedure will be summarized for the safety population. Summaries will 

 
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include incidence and counts overall for AEs and SAEs, by category, severity and by relationship to study 
device and /or protocol procedure.  
9.4.5 ADDITIONAL ANALYSES AND CONSIDERATIONS 
The following analyses will be conducted as supportive analyses to the primary analyses described in 
Section 9.4.3: 
Subgroup Analyses 
Primary performance measures will be presented separately by the following subgroups and evaluated 
for consistency:  
• 
BMI strata (Low ≤ 29; Medium > 29 and ≤ 35; High > 35 and ≤ 45)  
• 
Race 
• 
Study group (Antenatal and Enriched Hospital), defined as follows: 
o Antenatal – includes subjects evaluated per obstetric standard of care in the clinic/office 
environment and subjects completing research-only visits in a non-clinic setting with 
oversight by a healthcare professional. Subjects with premature rupture of membrane 
(PROM) will also be included.  
o Enriched Hospital – includes subjects in early (latent) phase of labor with suspected or 
confirmed uterine contractions, and subjects who are being induced for labor. 
Primary performance measures data will be analyzed for all subjects regardless of major protocol 
deviations, where available. 
Missing Data and Invalid Data 
Only valid synchronized data will be analyzed. Missing performance measurement data will not be 
imputed. Determination of invalid signals will be addressed by data management according to written 
work instructions.  
9.5 
SAMPLE SIZE JUSTIFICATION 
A sample size of N=80 evaluable subjects with an average of 60 minutes of comparative device data will 
provide adequate power to establish equivalence between M•care and standard of care in the primary 
performance measurements of FHR and MHR, and the secondary performance measurement of UC event 
sensitivity according to the success criteria and performance goals presented in Statistical Considerations 
Section 9.3. It is anticipated that up to 130 subjects may be recruited to allow for inability of approximately 
30% of subjects to enter the Monitoring Session phase of the study. 

 
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Background 
Mhajna et al reported the mean difference and (95% LOA) [SD] between INVU and standard of care 
reference CTG for FHR and MHR measurements as -0.30 bpm (-8.84, 8.24) [SD=4.36] and 0.28 (-5.30, 5.86) 
[SD=2.85], respectively.1 Furthermore, Hayes-Gill et al2 and Mhajna et al3,4  reported positive agreement 
(e.g., sensitivity) rates vs IUPC in uterine contraction events of 88%. 
Power Considerations 
In this study, each recording session will last for a minimum of 60 minutes and no longer than 120 minutes 
yielding an assumed minimum of 30 observations per subject for FHR and MHR, and an average of 3 UC 
events per subject. FHR and MHR are assumed to be normally distributed, with FHR mean (SD) of -0.3 
(4.4), MHR mean (SD) of 0.3 (3).  UC sensitivity is assumed to be distributed binary, with UC sensitivity of 
90%. For all measurements, the within subject correlation is assumed to be 0.5 and compound symmetric.  
Based on these assumptions and simulations with SAS 9.4 statistical software of MMRM and bootstrap 
resampling analyses as described above in Statistical Considerations Section 9.4, N=80 evaluable subjects 
will provide greater than 80% power (using either statistical method MMRM or bootstrap resampling) to 
establish equivalence between M•care and standard of care in each of the primary performance 
measurements of FHR and MHR and UC event sensitivity according to the success criteria and 
performance goals presented in Statistical Considerations Section 9.3. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to each individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Consent forms will be Institutional Review 
Board (IRB)-approved and each subject will be asked to read and review the entire document. The trained 
study staff will explain the research study to the subject and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the subject’s comprehension of the purposes, procedures, 
and potential risks of the study and of their rights as research subjects.  Subjects will have the opportunity 
to carefully review the written consent form and ask questions prior to signing. The subjects should have 
the opportunity to discuss the study with their family or surrogates or think about it prior to agreeing to 
participate. The subject will sign the informed consent document prior to any procedures being done 
specifically for the study. Subjects will be informed that participation is voluntary and that they may 
withdraw from the study at any time, without prejudice. A copy of the informed consent document will 

 
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be given to the subjects for their records. The informed consent process will be conducted and 
documented in accordance with standard processes before the subject undergoes any study-specific 
procedures. The rights and welfare of the subjects will be protected by emphasizing to them that the 
quality of their medical care will not be adversely affected if they decline to participate in this study. The 
consenting process may be done remotely depending on site-specific regulations and capabilities. If 
remote consenting is employed, all required aspects of the consenting process must be documented and 
meet HIPAA privacy regulations. 
After identifying a subject who meets minimum eligibility criteria before collecting study data, the study 
will be explained in detail to the subject including: (1) that the study represents a research effort, (2) that 
participation is voluntary, and there is no penalty for withdrawal, (3) potential risks and benefits of 
participation, (4) the procedures to ensure privacy of their medical information, and (5) contact 
information for addressing additional concerns.  Subjects are informed of the purpose of the study and of 
their options to accept or refuse entry into the study.  Only with the full and complete understanding of 
the study, and signed informed consent, will the evaluation of the potential subject continue.  In 
accordance with 21 CFR parts 50 and 56, all subjects must provide written informed consent in accordance 
with each clinical site’s Institutional Review Board/Medical Ethics Committee (IRB/MEC).  A copy of the 
consent form from each center must be forwarded to Marani Health.  Approvals for continuation of the 
study at each clinical site must be obtained according to their local IRB/MEC requirements (at a minimum, 
annually). 
Foreign language consenting may be approved at the site per local rules. 
Subjects will receive remuneration following completion of study activities as set forth by the reviewing 
Institutional Review Boards (IRB).  
10.2 ETHICAL CONSIDERATIONS 
The investigator will ensure that this study is conducted in full conformity with the current revision of the 
Declaration of Helsinki, and with the regulations and guidelines of the FDA (all state/local regulations) and 
ISO 14155, whichever affords greater protection to the subjects. 
10.3 INSTITUTIONAL REVIEW BOARD (IRB)  
The study must have unconditional IRB approval in writing; language should be approved by local site 
IRBs. A copy of the Letter of Approval from the local IRB, which contains specific identification of the 
documents approved, must be received by Marani Health prior to site initiation.  
Any amendments to the protocol or subsequent changes to the informed consent form as a result of 
changes to the protocol and/or IFU approved by Marani Health must also be approved, as appropriate, by 
the IRB and documentation of this approval provided to Marani Health. Records of the IRB review and 

 
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approval of all documents pertaining to this study must be kept on file at the site by the investigator and 
are subject to regulatory authority and/or sponsor inspection during or after completion of the study.  
Continuing Review reports must be submitted to the IRB as required, as well as notification of completion 
of the study and a final report where applicable. A copy of all reports submitted to the IRB must be sent 
to the sponsor. 
10.4 PROTOCOL AMENDMENTS 
Major changes to the protocol should only be made by an approved protocol amendment. Protocol 
amendments must be approved by the Sponsor and each respective site’s IRB prior to implementation. 
10.4.1 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study subjects, investigator, sponsor and regulatory authorities.  
If the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform 
active study subjects, the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for 
the termination or suspension.   
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoints have been met 
• 
Determination of futility 
If suspended, the study may resume once concerns about safety, protocol compliance, and data quality 
are addressed, and satisfy the sponsor, IRB and/or FDA requirements. 
10.4.2 CONFIDENTIALITY AND PRIVACY  
Confidentiality will be ensured at the site and by the sponsor throughout the study. All subject data will 
be identified only by a subject identification number. A key will be kept at each study site connecting 
subject identification numbers to names/demographic information in a secure location; this key will not 
be sent to the sponsor but may be monitored at the site. After obtaining each subject’s consent, the 
investigator will permit the study monitor, independent auditor or regulatory agency personnel to review 
that portion of the subject’s medical record that is directly related to the study. No other medical 
identifying information or PHI will be collected. 

 
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10.4.3 FUTURE USE OF DATA  
After the study is completed, the de-identified, archived data will be stored electronically for future use 
by Marani. Permission to store data will be included in the informed consent.   
During the conduct of the study, an individual subject can choose to withdraw consent to have data used 
for future research.  
10.4.4 CLINICAL MONITORING 
Marani will conduct monitoring at participating clinical sites to ensure that all Investigators comply with 
the protocol and the signed Investigator’s Agreement.  Sites will be required to report any circumstances 
in which an Investigator deviates from the clinical protocol; corrective action will be taken as necessary. 
Monitoring will be completed per the monitoring plan and may include remote monitoring as the site 
allows. Complete study documentation will be maintained at each site for records verification. The 
coordinator and/or investigator should be available to answer questions or resolve data clarifications. 
Regulatory binder contents will also be monitored for completeness. 
10.4.5 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion.   
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks of the database will be generated.  The web-based integrated system monitors and tracks data 
quality, including missing information, forms and any data lag for entry (i.e., overdue forms).  In addition, 
the system reports the status of data quality both to the local center (at both a summary- and a subject-
level report) and to Marani. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted, and data are generated, documented (recorded), and reported in compliance with the 
protocol, Clinical investigation of medical devices for human subjects – Good Clinical Practice (ISO 
14155:2020 GCP), and applicable regulatory requirements.  
Each investigational site will provide direct access to all trial related source data/documents, and reports 
for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 

 
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10.4.6 DATA HANDLING AND RECORD KEEPING  
 
10.4.6.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. 
Hardcopies of the study visit worksheets (CRFs) will be provided for use as source document worksheets 
for recording data for each subject enrolled in the study.  Data recorded in the electronic case report form 
(eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
10.4.6.2 STUDY RECORDS RETENTION  
The investigator will maintain a comprehensive and centralized filing system of all relevant documentation 
in accordance with current standards and local rules. Investigators will be instructed to retain all study 
records required by Marani Health and regulatory authorities in a secure and safe facility with limited 
access for one of the following time periods based on notification from Marani Health:  
• 
A period of at least three years from last marketing authorization and notification from sponsor; 
or 
• 
A period of at least three years after discontinuation of clinical development of the investigational 
product as confirmed by Marani Health; or 
• 
Longer, if required by local regulations  
The investigator will request and receive written permission from Marani Health before disposal of any 
study records. Sites will provide written notification to Marani Health of any change in the location, 
disposition, or custody of the study files. 
All files must be disposed of according to local and federal rules. 
10.4.7 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol (ISO 14155:2020 GCP). The 
noncompliance may be either on the part of the subject, the investigator, or the study site staff. As a result 
of deviations, corrective actions are to be developed by the site and implemented promptly.  
It is the responsibility of the site investigator to use continuous vigilance to identify and report major 
deviations as defined by site reporting procedures.  All deviations must be addressed in study source 
documents and reported to Marani on the appropriate CRF.  Protocol deviations must be sent to the 

 
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reviewing Institutional Review Board (IRB) per their policies. The site investigator is responsible for 
knowing and adhering to the reviewing IRB requirements and policies. 
10.4.8 TRIAL REGISTRATION 
This trial will be registered with ClinicalTrials.gov. Study progress and results will be posted there as 
required.  
10.4.9 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical.  Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest 
will be required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial and per the IRB. Potential conflicts are reviewed per local site guidance 
and recommendations will be made for managing conflicts.  
10.5 ABBREVIATIONS 
 
Abbreviation 
Term 
ACOG 
American College of Obstetricians and Gynecologists  
AE 
Adverse Event  
APP 
Proprietary Mobile Application  
BMI 
Body Mass Index  
BPM 
Beats Per Minute 
BT 
Bluetooth  
BLE 
Bluetooth Low Energy 
CCM 
Cloud Computing Module  
CE 
European Conformity  
CL 
Cervical Length  
CRC 
Clinical Research Coordinator  
CRF 
Case Report Form  
CTG 
Cardiotocography  
DPE 
Data Processing Engine  
IRB 
Institution Review Board  
ECG 
Electrocardiogram  

 
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Abbreviation 
Term 
EEG 
Electroencephalography  
EHG 
Electrohysterography  
EMG 
Electromyography  
EUM 
Electrical Uterine Myography  
FCC 
Federal Communications Commission  
FDA 
Food and Drug Administration  
FHR 
Fetal Heart Rate 
FSE 
Fetal Scalp Electrode  
GCP 
Good Clinical Practice 
GDM 
Gestational Diabetes mellitus 
HIPAA 
Health Insurance Portability and Accountability Act 
HTN 
Hypertension 
HW 
Hardware  
ICF 
Informed Consent Form  
IFU  
Instructions for Use 
IP 
Investigational Product  
IRB 
Institutional Review Board 
IUPC 
Intrauterine Pressure Catheters  
LOA 
Limits of Agreement 
M•CARE™ 
Marani Health M•care™ System 
M•CORE™ 
Marani Health M•core™ controller 
M•WRAP™ 
Marani Health M•wrap™ wearable band 
MA 
Mobile Application  
MD 
Medical Doctor  
ME 
Management Engine  
MHR 
Maternal Heart Rate  
NST 
Non-Stress Test  
PA 
Performance Analysis  
PCG 
Phonocardiography  

 
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Abbreviation 
Term 
PI 
Primary Investigator  
RTTI 
Run-Time Type Information  
SA 
Safety Analysis  
SAE 
Serious Adverse Event 
SW 
Software  
TOCO 
Tocodynamometry  
UA 
Uterine Activity  
UADE 
Unanticipated Adverse Device Effect 
UC 
Uterine Contractions  
 
10.6 DEFINITIONS 
 
Term 
Definition 
Adverse Event 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs in subjects, users, or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated. (ISO 
14155:2020, section 3.2) 
Device 
Deficiency 
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, usability, safety, or performance. Device deficiencies include 
malfunctions, use errors, and inadequacy in the information supplied by the 
manufacturer including labeling. This definition includes device deficiencies related 
to the investigational medical device or comparator. (ISO 14155:2020, section 3.19) 
Device 
Malfunction 
Failure of an investigational medical device to perform in accordance with its 
intended purpose when used in accordance with the Instructions for Use, study 
protocol, or Investigator’s Brochure. (ISO 14155:2020, section 3.33) 
SAE 
An adverse event that led to: 
a) Death 
b) A life-threatening illness or injury 
c) Permanent impairment of a body structure or body function including 
chronic diseases 
d) In-patient or prolonged hospitalization 
e) Medical or surgical intervention to prevent life-threatening illness or injury, 
or permanent impairment to a body structure or a body function 
f) Fetal distress, fetal death, a congenital abnormality, or birth defect including 
physical or mental impairment 

 
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Term 
Definition 
(ISO 14155:2020, section 3.45) 
Unanticipated 
Adverse Device 
Effect 
Any serious adverse effect 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, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), 
or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. (21 CFR 812.3(s)) 
 
10.7 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes with versions of the protocol, including a description of 
the change and rationale.  
Version 
Date 
Description of Change 
Brief Rationale 
B 
07JUL2021 
Initial IRB-approved version 
N/A 
C 
29DEC2021 
Addition of a third group to the study 
population to include a Research Visit 
group, defined as subjects scheduled 
for research visits in a non-clinic 
setting with oversight by a clinical 
practitioner. 
Inclusion of the Research 
group was done to reflect the 
non-clinic study setting 
D 
17FEB2022 
• Section 1.2 ‘Study Flow’ figure 
updated to revise step prior to the 
‘Place M·wrap’ to include reference 
to the IFU.  
• Revisions to Exclusion Criteria #2 & 
#7 
• Updates to Section 6.1 to clarify 
process flow  
• Section 10.5 updated to include 
abbreviation for Instructions for 
Use (IFU) 
• Appendix 12.1 ‘Study Flow’ figure 
updated as referenced in 1st bullet 
above 
Reference Instructions for Use 
(IFU) where applicable; 
revisions to Exclusion Criteria 
for consistency with IFU; 
clarify study administration 
process flow. 

 
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Version 
Date 
Description of Change 
Brief Rationale 
E 
22JUN2022 
• Added protocol agreement form at 
front of document 
Alignment with GCP 
• Synopsis and Section 5.4 updated 
to redefine group definitions 
Alignment with statistical 
analysis plan (Section 9); no 
changes to the overall study 
population or methods for 
recruitment/research conduct 
• Synopsis and Section 5.2 updated 
to add an additional exclusion for 
subjects with history of skin 
allergies to cosmetics and lotions 
Added to ensure exclusion of 
patients who may be allergic 
• Synopsis and various places 
throughout Sections 3 and 9 
updated to move UC sensitivity 
from primary to secondary 
endpoint 
Updated regulatory strategy 
• Synopsis and Sections 3 and 9 
updated throughout 
Consistency between sections 
• Added section 3.1, Objective 
Consistency with synopsis and 
Section 9 
• Removed reference to undefined 
term “Unanticipated Problems” 
throughout the document, replaced 
with the more appropriate term 
(e.g., adverse event, device 
deficiency) when applicable 
Consistent use of FDA and ISO 
14155:2020 GCP defined 
terminology  
• Section 7.1 updated to remove 
reference to subject replacement 
Replacements will not be 
utilized for this study 
• Section 8.3.1 updated to remove 
reference to 21 CFR 312 and clarify 
applicable medical device 
21 CFR 312 was written in 
error and is not applicable to 
medical device studies; 
medical monitor not 

 
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Version 
Date 
Description of Change 
Brief Rationale 
definitions, removed reference to 
medical monitor review 
necessary for a non-significant 
risk study 
• Section 8.3.2 updated to replace 
“failures and malfunctions” with 
“device deficiencies”  
Using preferred term per ISO 
14155:2020 GCP, which 
includes both device failures 
and malfunctions 
• Reference to ISO 14155:2020 GCP 
added where applicable throughout 
the document 
ISO 14155:2020, Clinical 
investigation of medical 
devices for human subjects – 
Good clinical practice, will be 
followed for this study 
• Section 10.4.5 updated to remove 
reference to Good Laboratory and 
Good Manufacturing Practices (GLP 
and GMP) 
GLP and GMP are out of scope 
for what clinical monitors will 
verify.  
• New Section 10.6 added to provide 
definitions of common safety 
terminology used throughout the 
document 
Consistency of terminology 
and compliance to common 
regulatory definitions 
• Added missing references and 
corrected errors in citations 
throughout the document, updated 
bibliography in section 11 
Accuracy of scientific rationale 
• Appendix 1 (Study Setup and 
Monitoring Flow) deleted 
Redundant with Section 1.2 
• Added appropriate references to 
tables, figures, and appendices 
throughout the document 
• Minor corrections and deletion of 
redundant phrases throughout the 
document 
Readability, clarity, and 
consistency across the 
document  

 
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Version 
Date 
Description of Change 
Brief Rationale 
F 
26-SEP-2022 
• Correction to study center name in 
synopsis  
Error correction 
• Changed “clinical practitioner” to 
“healthcare professional” 
throughout the document 
Provide clarity of oversight of 
research-only study center 
• Inclusion criterion #7 changed from 
“≤ 130 cm” to “≤ 135 cm”  
Error – criterion corrected to 
match M•wrap sizing chart 
• Corrected wording throughout to 
clarify differences between 
research-only visits and visits 
occurring in a clinical setting 
Accuracy of requirements 
based on type of study center 
• Section 10.1: Removed “$70” as the 
subject renumeration amount 
Renumeration type will be set 
forth by the reviewing IRB and 
may vary across study centers 
G 
13-Dec-2022 
• Synopsis and Section 9.5: Updated 
total enrollment number from 115 
to 130 
Increase in total enrollment 
maximum to allow for 
flexibility in anticipated 30% 
fallout rate.  
 
 

 
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11 REFERENCES  
1. 
Mhajna, M. et al. Wireless, remote solution for home fetal and maternal heart rate 
monitoring. Am J Obstet Gynecol MFM 2, (2020). 
2. 
Hayes-Gill, B. et al. Accuracy and Reliability of Uterine Contraction Identification Using 
Abdominal Surface Electrodes: https://doi.org/10.4137/CMWH.S10444 5, CMWH.S10444 
(2012). 
3. 
Mhajna, M., Reches, A., Zahar, Y. & Schwartz, N. 401 Amplitude-modulation of maternal 
electrocardiography and phonocardiography as a novel method for wireless non-invasive 
uterine monitoring. American Journal of Obstetrics & Gynecology 224, S259 (2021). 
4. 
Schwartz, N. et al. Novel uterine contraction monitoring to enable remote, self-
administered nonstress testing. Am J Obstet Gynecol 226, 554.e1-554.e12 (2022). 
5. 
Kassebaum, N. J. et al. Global, regional, and national levels and causes of maternal 
mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 
2013. Lancet 384, 980 (2014). 
6. 
Creanga, A. A., Bateman, B. T., Kuklina, E. v. & Callaghan, W. M. Racial and ethnic 
disparities in severe maternal morbidity: a multistate analysis, 2008-2010. Am J Obstet 
Gynecol 210, 435.e1-435.e8 (2014). 
7. 
Howell, E. A. Reducing Disparities in Severe Maternal Morbidity and Mortality. Clin Obstet 
Gynecol 61, 387–399 (2018). 
8. 
Moaddab, A. et al. Health Care Disparity and Pregnancy-Related Mortality in the United 
States, 2005-2014. Obstet Gynecol 131, 707–712 (2018). 
9. 
Boyd, L. C. et al. Pregnancy-Associated Mortality New York City Department of Health and 
Mental Hygiene Bureau of Maternal, Infant and Reproductive Health Pregnancy-
Associated Mortality Review Project Team. 
10. 
Mortality in the United States. http://dx.doi.org/10.1056/NEJM184002260220306 22, 46–
47 (2010). 
11. 
Pillai, M. & James, D. The development of fetal heart rate patterns during normal 
pregnancy. Obstet Gynecol 76, 812–816 (1990). 
12. 
Shuffrey, L. C. et al. Fetal heart rate, heart rate variability, and heart rate/movement 
coupling in the Safe Passage Study. J Perinatol 39, 608–618 (2019). 
13. 
Cohen, W. R. et al. Accuracy and reliability of fetal heart rate monitoring using maternal 
abdominal surface electrodes. Acta Obstet Gynecol Scand 91, 1306–1313 (2012). 

 
 
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14. 
Reinhard, J. et al. Intrapartum signal quality with external fetal heart rate monitoring: a 
two-way trial of external Doppler CTG ultrasound and the abdominal fetal 
electrocardiogram. Arch Gynecol Obstet 286, 1103–1107 (2012). 
15. 
American College of Obstetricians. Practice bulletin no. 116: Management of intrapartum 
fetal heart rate tracings. Obstet Gynecol 116, 1232–1240 (2010). 
16. 
Easterling, T., Benedetti, T., Schmucker, B. & Millard, S. Maternal hemodynamics in 
normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol 76, 1061–
1069 (1990). 
17. 
van Oppen, A. C. C., van der Tweel, I., Alsbach, G. P. J., Heethaar, R. M. & Bruinse, H. W. A 
longitudinal study of maternal hemodynamics during normal pregnancy. Obstet Gynecol 
88, 40–46 (1996). 
18. 
Sherman, D. J. et al. Characteristics of maternal heart rate patterns during labor and 
delivery. Obstet Gynecol 99, 542–547 (2002). 
19. 
van Veen, T. R., Belfort, M. A. & Kofford, S. Maternal heart rate patterns in the first and 
second stages of labor. Acta Obstetricia et Gynecologica Scandinavica 91, 598–604 (2012). 
20. 
Odendaal, H., Groenewald, C., M. Myers, M. & P. Fifer, W. Maternal heart rate patterns 
under resting conditions in late pregnancy. Trends Res 1, (2018). 
21. 
Lu, M. J. et al. Sample Size for Assessing Agreement between Two Methods of 
Measurement by Bland-Altman Method. Int J Biostat 12, (2016). 
  
 
 

 
 
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12 APPENDICES 
APPENDIX 1 – M•WRAP CONFIGURATION FOR CONCURRENT CTG USE 
Marani Health proposes a series of performance data testing to support the substantial equivalence 
determination. The M•wrap capabilities of accurately recording with high fidelity the FHR, MHR and UC 
will be determined by comparing our system to the reference device, the Philips Avalon FM 20, FM30, 
FM40, or FM50.  
A segment of the M•wrap compression garment fabric will be cut out to enable simultaneous recording 
of FHR, MHR and UC with the M•wrap and the Philips Avalon FM 20, FM30, FM40, or FM50. The below 
image is a representative graphic of the M•wrap and possible locations for the TOCO and Doppler 
Transducers.   
 
These TOCO and Doppler transducers will be placed in the available garment material and will not affect 
the integrity of the electrodes and wires.  The M•wrap contains spaces consisting of textile fabric only 
which is around the inlay section in which CTG transducers can be located without interfering with the 
device. The figure below shows possible placements for the CTG transducers, labeled A – F. There are six 
broad positions within the garment that can accommodate CTG placement, with some flexibility in each 
area that will allow for placement optimization.