Hysterectomy Vs Partial Myometrial Resection for Placenta Accreta Spectrum (PAS). A Feasibility Study of a Randomized Controlled Clinical Experiment (RCT-PAS)
Phase: NA
Conditions: Placenta Accreta
Sponsor: Fundacion Clinica Valle del Lili

  
 
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HYSTERECTOMY VS PARTIAL MYOMETRIAL RESECTION FOR 
PLACENTA ACCRETA SPECTRUM (PAS).  A FEASIBILITY STUDY OF A 
RANDOMIZED CONTROLLED CLINICAL EXPERIMENT (RCT-PAS) 
 
 
 
 
Principal investigators: 
Albaro José Nieto-Calvache1 
 
 
 
 
 
1 Departamento de Gineco Obstetricia, Clínica de Espectro de Acretismo Placentario, 
Fundación Valle del Lili, Cali, Colombia.  
 
FUNDACIÓN VALLE DEL LILI, CALI, COLOMBIA 
 SEPTEMBER 2021 
 
 
 
 
 
 

  
 
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1. SYNOPSIS 
Data category 
Information 
Registration - Study ID 
Number 
Clinical Trial.gov assigned number 
NCT05013749 
Registration Date 
August 18, 2021 
Principal Sponsor 
Centro de Investigaciones Clínicas – Fundación Valle del Lili. Cali, 
Colombia 
Contact for public 
consultation: 
+57 (2) 331 90 90 Ext. 4022 
Contact for scientific 
consultation: 
Albaro José Nieto-Calvache 
albaro.nieto@fvl.org.co  
Public title: 
RCT-PAS 
Scientific Title: 
Hysterectomy vs partial myometrial resection for placenta accreta 
spectrum  (PAS).  A feasibility study of a randomized controlled 
clinical experiment (RCT-PAS) 
Recruitment coordination 
center: 
Fundación Valle del Lili. Cali, Colombia  
Recruitment centers: 
3  
Health Condition or 
Problem 
Placenta Accreta Spectrum  (PAS)  
Study Type 
Feasibility study of an open-label (non-blinded), randomized, 
controlled, multicenter clinical trial. 
Primary objective 
To evaluate the feasibility of the parallel experimental design, 
willingness of eligible patients to participate, and outcome measures 
for conducting a randomized phase III clinical trial comparing 
partial myometrial resection with hysterectomy in patients with 
PAD, conducted at 3 different centers, including the Fundación 
Valle del Lili, over a 24-month period. 
Specific objectives 
 
 
- 
 Measure the proportion of eligible patients who agree to 
participate in this comparison. 
- 
To measure the percentage of screening failure.  
- 
Describe the confirmation of the presence or absence of 
placental accreta spectrum in each case. 
- 
To identify the degree of variability between the different 
methods of measuring intraoperative bleeding in each of the 
techniques. 

  
 
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Secondary objective 
Clinical and sociodemographic characterization of the patient.  
To identify the characteristics of the patient's current pregnancy.  
To describe the clinical outcomes of interest in patients randomized 
to hysterectomy or partial myometrial resection.  
To categorize the severity of surgical complications according to the 
Clavien Dindo classification. 
Study design 
Feasibility study of randomized, controlled, multicenter clinical 
experiment on the use of partial myometrial resection vs. 
hysterectomy. 
Intervention group 
Patients with a confirmed diagnosis of PAD (See Appendix 2, 
Definition of a confirmed case of PAD) Partial myometrial 
resection. 
Control 
Patients with a confirmed diagnosis of PAD (See Annex 2, 
Definition of a confirmed case of PAD). Hysterectomy. 
Population 
Pregnant women with a prenatal ultrasound or MRI diagnosis of 
PAD (See Appendix 2: Definition of suspected case of PAD), who 
will be taken to surgery to treat this disease. 
Inclusion Criteria 
- 
Pregnant woman older than 18 years. 
- 
History of previous cesarean section and previous placenta 
previa.  
- 
Prenatal diagnosis by ultrasound or MRI of PAS (See 
Appendix 2: Definition of suspected case of PAS), 
regardless of the suspected degree of severity of the 
disease. 
- 
Requirement of surgical management of placental accreta 
on a scheduled basis.  
- 
Patients without active vaginal bleeding in the period 
immediately prior to surgery (Patients admitted to the 
operating room without active bleeding). 
Exclusion Criteria 
Women without previous living children. 
Sample Size 
60 participants 
Randomization method 
Permuted blocks of 4 and 6, stratified by center 
Primary outcomes: 
- Proportion of eligible patients who agree to participate in the study. 
- Percentage of screening failure. 
- Percentage of patients assigned to each arm of the study.  
- Percentage of patients with cross over between assigned arms of the 
study.   
- Number of subjects completing follow-up at 42 days postpartum. 

  
 
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Secondary outcomes: 
- Maternal death  
- Intraoperative bleeding volume measured in mL.  
- Blood component transfusion requirement, median transfusion of 
red blood cell units (RBCs), platelets, fresh frozen plasma, 
cryoprecipitate and fibrinogen. 
- Compliance with at least one WHO Near Miss criterion (See 
Appendix 1). 
- Ureteral lesions.  
- Bladder lesions 
- Need for surgical reintervention.  
- Days of hospital stay in Intensive Care Unit. 
- Days of general and postoperative hospital stay. 
- Use of uterine tamponade with hydrostatic balloons.  
- Presence of supra fascial hematoma.  
- Presence of postoperative ileus.  
- Vital status of the newborn.  
- Weight of the newborn. 
Statistical analysis 
It will be performed according to the principles of intention-to-treat 
analysis. Descriptive statistics will be used to summarize the 
feasibility results. According to the CONSORT guidelines for 
feasibility experiments, efficacy tests are not recommended, because 
the study is not designed to detect differences between types of 
surgery, therefore, for clinical outcomes the analyses will focus 
mainly on descriptive analyses using mean (standard deviation) or 
median (interquartile range) for continuous outcomes and absolute 
frequencies and percentages for categorical outcomes. For the 
specific objective of the degree of variability of the bleeding 
methods, the coefficient of variation of each method within the 
surgical techniques will be calculated. The STATA software version 
14.0 ® will be used. 
 
Key Words 
 
Placenta accreta spectrum, Hysterectomy, resective reconstructive 
treatment. 
 

  
 
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Amendment  
1.0 
Rationale 
 
Table of Contents 
Included 
Synopsis 
Included 
6.3 Specific objectives 
Objective 1 is deleted: To evaluate the willingness of the team of 
gynecologists to recruit patients for a clinical experiment. This is 
eliminated because it would be 100% because the team of intensivist 
gynecologists of the placental accreta spectrum clinic have signed the 
log of responsibilities.  
Compliance with this agreement is difficult to measure because 
women who might be eligible are not known and were not identified 
by gynecologists.  
Objective 4 is deleted: To measure the frequency and describe the 
cross-over ratios in each group using random assignment of the 
intervention. This is eliminated because there is only one cross-over 
ratio. This ratio is described in section 9.4 Study groups of the 
protocol.  
Objective 5 is modified: The purpose of this objective is clarified, 
which is to measure how concordant the methods for measuring 
bleeding are. The secondary clinical outcomes or complications are 
by clinical diagnosis and there is no doubt about them. 
Objective 6 is deleted: To identify the administrative barriers to the 
performance of the randomly assigned procedure is eliminated 
because in this study there are no administrative withdrawals. 
Objective 7 is deleted: To evaluate the comparability and 
generalizability of the sample of patients studied is eliminated 
because in this type of study the patients are highly selected, with very 
strict criteria. Therefore, the comparability and generalizability is 
very low. 
The objective is added to describe the confirmation of the presence or 
absence of placental accreta spectrum in each case. 
6.4 Secundary objectives 
The objective is included: To categorize the severity of surgical 
complications according to the Clavien Dindo classification. 
8.2 
Secondary 
outcome 
measures 
New secondary outcomes that were not contemplated in the previous 
version of the protocol are included. 
9.6 Sample size 
The sample size is specified according to the estimated recruitment 
rate for each center, the proposal is: 36 patients for Indonesia, 12 
patients for Argentina and 12 patients for Colombia. 
9.15 Interim analysis plan 
The interim analysis plan is modified, it is proposed to perform this 
analysis when 10 patients have been randomized, proportional to the 

  
 
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expected recruitment rate: 60% for the largest recruiter and 40% 
between the other two institutions. 
9.10 Procedures flow chart 
Included. 
10. 1.  Data collection 
The affiliation of the Biomedical Research Ethics Committee is 
clarified: the Ethics Committee (IRB) belongs to the Fundación Valle 
del Lili and is independent of the Clinical Research Center. 
10.3 Data quality monitoring -The research team is appointed as an independent clinical monitor 
according to Good Clinical Practice guidelines. 
-Data verification times are adjusted to the recruitment rate. 
-Monitoring plan is defined. 
11.2 Informed Consent 
Typing error corrected, this protocol does not contemplate Legal 
Representation for the participants. 
12.6 Safety and Adverse 
Event Evaluation Committee 
Statistician independent of the research group is appointed according 
to Good Clinical Practice guidelines. 
Appendix 3 
Possible participant identification is deleted, box for eligibility 
confirmation is increased.. 
Appendix 4 
Redesigned format for screening and randomization registry. 
Appendix 5 
The functions of the clinical coordinator of the study are adjusted, the 
figure of the sub-investigator is added. 
Appendix 6 
Redesigned format, added evaluation of the intensity of the event by 
the principal investigator 
Appendix 9 
Telephone contact form is designed for a follow-up visit at 42 days 
postpartum. 
 
Amendment 
2.0 
6.3 Specific objectives 
The objective is added to describe the confirmation of the 
presence or absence of placental accreta spectrum in each case. 
6.4 Secundary objectives 
The objective is included: To obtain a photographic and filmic 
record of the PAS prenatal diagnostic ultrasound, surgery and 
histopathology of all included cases, in order to verify the 
presence or absence of PAS in each patient. 
9.7.1 Recruitment strategy: 
Selection 
A paragraph of the recruitment strategy is modified to clarify the 
collection of photos and videos of prenatal ultrasound, surgery 
and histology of each case.  
9.10 Procedures flow chart 
The order of the follow-up visits provided for in the procedures 
flowchart is modified. 

  
 
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9.14 Statistical analysis plan The statistical analysis plan is modified, including the coefficient 
of variation of the methods for measuring intraoperative bleeding. 
9.15 Interim analysis plan 
The specification of performing the analysis proportional to the 
expected recruitment rate is eliminated. 
10. 1.  Data collection 
It is specified that information about the result of the 
histopathological study of the surgical specimen will be 
collected.  
10.2.3 Medical visit between 7 
and 12 days 
The option of follow-up between 7 and 12 days through 
telemedicine has been added. 
15. Variables tables 
The following variables are added: confirmation of PAS by 
histopathology, degree of invasion of PAS according to 
histopathology.  
The numbering of the response options for the dichotomous 
variables was corrected, it was clarified that admission to the ICU 
is related to PAS, and the wording of some variables was 
corrected. 
16. White tables 
The pertinent corrections are made in white tables taking into 
account the corrections made in the variable tables.  
Table 5 represents the coefficient of variation of the methods for 
measuring intraoperative bleeding, is added. 
Appendix 4  
The screening and enrollment format of the study is modified, the 
name of the institution is added as the title of the table, the date 
of screening, age and assignment group are added for each patient 
according to inclusion and exclusion criteria. 
Appendix 5 
The role is added to the principal investigator and co-investigator 
of taking photos during the surgical procedure.  
The option of follow-up between 7 and 12 days through 
telemedicine has been added. 
The deadlines for recording variables in Red Cap® have been 
modified to a suggested period of 48 hours and maximum 7 days. 

  
 
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The name of the Clinical Coordinator of the study is modified, 
Dr. Lina María Vergara retires and Dr. Stiven Sinisterra Díaz 
joins the team.  
The description of the procedure for disclosure of randomization 
by the clinical coordinator is modified. 
Added role for the study coordinator to provide support to the PI 
in the collection of PAS prenatal diagnostic ultrasound photos 
and histology. 
The functions of the clinical coordinator of the study are adjusted, 
the figure of the sub-investigator is added.  
Appendix 10: Standardized 
surgical 
technique 
manual 
and photographs 
A detailed step-by-step description of both techniques to be 
implemented in the study and the technical specifications for 
taking photographs and videos are included in the surgical 
technique manual. 
 
1. Introduction:  
Placenta accreta spectrum (PAS) is an increasingly frequent pathology, which is probably 
related to the increased rates of cesarean sections throughout the world1. This is a 
potentially dangerous condition associated with maternal risks, such as massive blood 
loss, pelvic organ damage (urinary tract or bowel), and occasional maternal mortality. 
Prenatal imaging detection was reported to have a high degree of accuracy in a cohort of 
women with an anterior cesarean delivery and placenta previa2,3. However, both 
ultrasound and magnetic resonance imaging have variable diagnostic precision depending 
on who performs the study, reporting failures in both diagnostic modalities4. Thus, even 
a quarter of patients undergoing surgery for suspected PAS end up having another 
diagnosis5.  
There are multiple management options, but the ideal treatment modality is unknown. 
The most widely used definitive treatment in the world is cesarean section - elective 
hysterectomy6. However, some investigators have reported that partial myometrial 
resection and uterine repair are successful in the vast majority of cases7. 
Even though there are multiple publications about conservative surgical management 
techniques in different populations, one of them being the partial resection of the 
myometrium followed by uterine repair (a technique called resective reconstructive 
surgery), the international management guidelines for PAS only include this alternative 
as an option in selected cases. Probably due to the little diffusion of the technique and the 

  
 
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need for specific training in it. However, something similar happens with hysterectomy 
for PAS. 
 
However, something similar happens with hysterectomy for PAS. It can be thought that 
any gynecologist is qualified to perform a hysterectomy for PAS since he performs 
postpartum hysterectomy for other etiologies; This is an incorrect premise since PAS 
hysterectomy requires competencies only achieved after extensive training. Additionally, 
partial resection of the myometrium involves the same interventions necessary to perform 
a hysterectomy, only organized in a different way, which probably simplifies the 
procedure in some cases. 
Since the most accepted technique worldwide is hysterectomy, and there is a belief that 
PAs affects the entire uterus, with no option of preserving this organ; It can be argued 
that partial myometrial resection is used in less severe cases of PAS and that more severe 
cases require a cesarean hysterectomy. Partial resection may be considered a useless 
strategy in severe cases. It can also be argued that the higher frequency of maternal 
complications associated with cesarean section hysterectomy may reflect the greater 
severity of the disease rather than the treatment modality itself. However, there are no 
reports of a direct comparison of these two surgical techniques and although the groups 
that use partial resection see important benefits over hysterectomy, a prospective study 
with an appropriate design is necessary to clarify which procedure is associated with 
better clinical results. 
2. Theoretical framework:  
Cesarean section followed by hysterectomy is the treatment choice in most centers that 
treat patients with PAS8. However, since 1998 the surgical treatment of PAS with uterine 
preservation has been described9 and a series of 248 patients with PAS has recently been 
published, finding that uterine preservation was possible in 81% of the cases7. 
This surgical technique involves a partial myometrial resection, that is, the resection of 
the myometrium affected by the abnormal invasion of the placenta. In general, it is only 
a part of the uterus, finding the rest of the myometrium free of PAS and susceptible to 
conservation. The main objective of this surgical technique is not the preservation of the 
uterus. It seeks to improve clinical results (less bleeding, less surgical time, less risk of 
ureteral injury, etc.), however, the conception that it is only necessary to resect a part of 
the uterus that is affected by PAS (and not the entire organ), allows to obtain an additional 
result: the preservation of the uterus. Avoiding a hysterectomy not only allows new 
pregnancies in the patient but also reduces blood loss (there is a volume of blood that is 
drawn together with the uterus during the hysterectomy) and reduces the extent of pelvic 
dissection required to carry out the surgery. 

  
 
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Although international consensus includes partial myometrial resection among the 
possible management options for PAS, it is almost always considered that it should be 
reserved for special cases, emphasizing the need for specific training in the technique10. 
Even though hysterectomy adequately solves the problem of PAS, it exposes the patient 
to morbidity inherent in the extensive pelvic dissection required to isolate the uterus from 
the other pelvic structures prior to removal. Among these morbidities are bladder and 
ureteral injuries11. Hysterectomy makes new pregnancies impossible and has also been 
linked to alterations in ovarian function. 
In the study carried out by Palacios Jaraquemada7, 20% of the patients required a 
hysterectomy. The experience in our center shows that a hysterectomy was performed in 
72% of patients between 2016 and 202012. 
Taking into account that most cases of PAS (64.6 %%) are cases considered "less severe", 
that is, placenta accreta (not increta or percreta)5 and that most patients (88%) have 
involvement of the upper part of the uterine segment or sector 1 of uterine vascularization 
(“S1”)13, it is easy to wonder if it is necessary to resect the entire uterus (hysterectomy) 
when only a portion of this organ is affected. 
It has been shown that, if the placenta accreta spectrum affects the anterior wall of the 
uterus and a portion of healthy myometrium is preserved at least 2 cm cephalad to the 
cervix, it is possible to perform a partial resection of the myometrium (resecting the 
portion of myometrium affected by PAS) and reconstruct the remaining myometrium 
(free of placenta accreta), preserving the uterus7. Fortunately, most patients with PAS  
meet these requirements and are candidates for the partial myometrial resection 
technique5,7. 
It has also been reported that after basic training and thanks to inter-institutional 
collaboration facilitated by telemedicine, it is possible to safely perform the partial 
myometrial resection technique in centers that initially only perform hysterectomy14. 
These centers that recently use partial resection can achieve a frequency of uterine 
preservation in patients with confirmed PAS, between 9% and 42%. This lower frequency 
of conservation when comparing centers that recently use the technique and those with 
more time to perform this type of surgery7, probably has to do with the experience 
applying this technique (“training curve”). 
Among the benefits of partial myometrial resection, over hysterectomy, are: 
1. Preservation of fertility 
2. Performing a less extensive surgery 

  
 
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3. Probably less blood loss 
4. Total preservation of ovarian perfusion 
5. Opportunity for differential treatment for cases that ultimately did not have PAS, 
despite a wrong prenatal diagnosis. In some patients, the diagnosis of PAS is 
suspected by ultrasound, but during laparotomy, it is found that they did not have 
this diagnosis (false positive of prenatal images). When, after fetal extraction, a 
hysterectomy is immediately carried out, it is possible to extract uteri that finally 
do not have PAS (22.6%)5 Partial myometrial resection requires a dissection of 
the vesicouterine space before fetal extraction, so that the surgeon can observe the 
entire anterior face of the uterus, approaching in a better way the definitive 
diagnosis, even before extracting the baby. 
Many observational studies describe good results with uterine preservation techniques. In 
March 2019, 25 publications on conservative surgical management in PAS were found, 
with more than 700 cases of successful uterine preservation14. All these studies were 
observational and retrospective, using different uterine preservation techniques. 
There are many useful clinical variables to evaluate the effectiveness of a certain PAS 
management technique. Observational studies of single or multicenter cohorts report, 
among other variables, the volume of blood loss, the frequency of transfusions, the 
number of blood components transfused, the frequency of operative complications, the 
surgical time, the need for additional surgeries, the time postoperative hospitalization, 
etc7,11,12,13,4,15,16. Some of these variables are directly influenced by the clinical status of 
the patient before surgery or the postoperative management habits of the center where the 
surgery is carried out (duration of postoperative hospitalization, frequency of 
transfusions) and others have a frequency of very low presentation so that its analysis 
would demand population sizes that are difficult to manage (ureteral injuries, 
reoperations). Therefore, it is proposed that the volume of intra-surgical bleeding is the 
variable to evaluate as the primary outcome in a definitive clinical experiment. 
3. Rationale 
The most appropriate treatment modality for women diagnosed with PAS is uncertain, 
the most widely used is cesarean section followed by hysterectomy. This technique is 
associated with high volumes of bleeding and operative complications, such as urinary 
tract injuries4. Partial resection of the myometrium has been reported to be associated 
with a lower probability of surgical damage to pelvic organs15. 
This lower rate of complications may be due to a selection bias since it could be thought 
that at least in some patients with not very severe affectations (those with placenta accreta 
and affectation of the upper part of the uterine segment S1), it is possible to perform 
surgery less extensive (partial resection of the affected myometrium) and preserve 
fertility. While the most severe cases (placenta increta, percreta, or involvement of the 

  
 
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lower part of the uterus or sector 2 of uterine vascularization) are more frequently taken 
to hysterectomy. 
Observational studies are unlikely to eliminate selection bias. The controversy can only 
be resolved by conducting a randomized controlled experiment in which women with a 
prenatal diagnosis of PAS are randomly assigned to undergo hysterectomy or partial 
myometrial resection as the intended treatment modality. This type of study would 
probably require a high number of patients and the participation of several hospitals that 
apply the same surgical technique. Considering that the international guidelines for the 
management of PAS make partial myometrial resection a technique reserved for a select 
group of patients, some centers refrain from implementing this type of technique and that 
there are not many centers in the world that do so practice. 
The studies published to date evaluating partial myometrial resection are retrospective 
and observational in nature7,14,15. Although the patients who undergo this type of surgery 
have been compared with a group of women who finally underwent a hysterectomy after 
partial resection has been attempted14,15,it is not possible to characterize in these 
publications two comparable groups (myometrial resection partial vs hysterectomy as 
management chosen and executed from the beginning of the surgery). 
Since a “head-to-head” comparison between hysterectomy and partial myometrial 
resection has never been performed previously, there are insufficient data to define a 
sample size necessary for conducting a definitive randomized clinical trial. It is therefore 
necessary to initially carry out a feasibility study to verify that all the procedures outlined 
in the protocol (to be carried out later) are viable. This feasibility study will also allow 
the collection of clinical data from both arms of the study that will allow planning a future 
definitive randomized clinical experiment. 
 
4. Research question: 
Is it possible to recruit, randomize, intervene, and measure outcomes of interest in patients 
with PAS as part of a clinical experiment comparing two PAS surgical techniques 
(hysterectomy vs. partial myometrial resection) in a period of 24 months or less? 
5. Objective: 
6.1.Primary objective: To evaluate the feasibility of the parallel experimental 
design, the willingness to participate of eligible patients, and the outcome 
measures for conducting a randomized phase III clinical experiment 
comparing partial myometrial resection with hysterectomy in patients with 
PAS, carried out in 3 different centers, including Fundación Valle del Lili, in 
a period of 24 months. 

  
 
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6.2.Specific objectives: 
1. To measure the proportion of eligible patients who agree to participate in this 
comparison. 
2. To measure the percentage of screening failure.  
3. To describe the confirmation of the presence or absence of placental accretenotic 
spectrum in each case.  
4. To identify the degree of variability between the different methods of measuring 
intraoperative bleeding in each of the techniques. 
6.3.Secondary objectives:  
1. Clinical and sociodemographic characterization of the patient.  
2. To identify the characteristics of the patient's current pregnancy.  
3. To describe the clinical outcomes of interest in patients randomized to 
hysterectomy or partial myometrial resection.  
4. To categorize the severity of surgical complications according to the Clavien 
Dindo classification.  
7. Hypothesis 
7.1.Primary hypothesis: It is possible to recruit, randomize, operate and follow-up 
patients recruited for an experiment comparing two surgical techniques in PAS 
(Hysterectomy Vs Partial myometrial resection) in a period of 24 months or less.  
8. Outcomes measures/endpoints:   
8.1.Primary endpoints:  
- 
Proportion of eligible patients who agree to participate in the study. 
- 
Screening failure percentage 
- 
Percentage of patients assigned to each arm of the study. 
- 
Percentage of patients with crossover between assigned study arms.   
- 
Number of subjects who complete follow-up at 42 days postpartum. 
8.2.Secondary endpoints:  

  
 
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- 
Maternal death 
- 
Intra-surgical bleeding volume measured in mL. 
- 
Blood component transfusion requirement, median transfusion of red blood cell 
units (RBCU) 
- 
Compliance with at least one WHO Near Miss criterion (See Appendix 1) 
- 
Ureteral injuries. 
- 
Bladder injuries 
- 
Need for surgical reoperation. 
- 
Admission to the Intensive Care Unit. 
- 
Days of post-operative hospital stay. 
- 
Use of uterine tamponade with hydrostatic balloons. 
- 
Presence of supra fascial hematoma  
- 
Presence of postoperative ileus 
- 
Vital status of the newborn  
- 
Weight of the newborn 
9. Methods: 
9.1.Study design: Feasibility study of a randomized, controlled, multicenter clinical 
experiment on the use of partial myometrial resection vs hysterectomy. 
It is expected to have the participation of 2 institutions invited and led by: 
Hospital Universitario CEMIC (Buenos Aires, Argentina)- Dr José Miguel 
Palacios Jaraquemada.  
Dr. Soetomo Academic General Hospital, Universitas Airlangga, (Surabaya, 
Indonesia)- Dr Rozi Aditya Aryananda 
The 3 institutions will use the same protocol (they will apply the same surgical technique 
and carry out the same information recording activities), but the randomization will be 
stratified for each site to ensure the same number of participants for each arm of the study 
at the 3 sites. 

  
 
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9.2.Study population:  Pregnant women with a prenatal ultrasound or magnetic 
resonance diagnosis of PAS (See Appendix 2: Definition of a suspected case of PAS), 
who will be taken to surgery to treat this disease at Fundación Valle del Lili and the 
institutions invited to participate 
 
9.3.Study groups:  
 
- 
Patients with a confirmed PAS diagnosis (See Appendix 2, Definition of 
confirmed PAS case) who will undergo partial myometrial resection. 
 
Although it has been reported that this type of surgery is viable in case of 
involvement of the anterior portion of the uterus, with a healthy myometrium 
of at least 2cm cephalad to the cervix. Our study suggests that partial 
myometrial resection should be attempted in all patients randomized to this 
intervention. Partial myometrial resection may not be feasible in some cases and 
the patient will receive a hysterectomy. The attempted partial myometrial 
resection does not imply a greater risk of bleeding for the patient, since having 
previously performed the vesicouterine dissection, vascular control techniques 
are readily available that can be applied in the event that the myometrial 
resection is unsuccessful, and a hysterectomy can be performed without 
exposing the patient to an increased risk of bleeding. 
 
- 
Patients with a confirmed diagnosis of PAS (See Appendix 2, Definition of a 
confirmed PAS case) who will undergo hysterectomy. All patients randomized 
to this intervention will receive a hysterectomy, regardless of the extent or 
severity of injury found at laparotomy. 
 
Both groups of patients will receive standard postoperative care (monitoring and 
hemodynamic, respiratory, metabolic support and in general the management described 
for this intervention) 
 
9.4.Selection of participants:  
 
Women with a previous cesarean section, anterior placenta previa, and imaging 
(ultrasound or MRI) with signs suggestive of PAS will be eligible to participate (See 
Appendix 2: Definition of a suspected PAS case). Informed consent will be requested 
from these patients prior to surgery. Considering that these are pregnant women, the 
participation of the husband or spouse will be included in the informed consent (Appendix 
7). In the event that the patient does not have a husband or spouse, the "Declaration of 
mother head of the family" will be filled out (Appendix 8).  
 

  
 
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Randomization will be carried out before starting the surgical procedure, with the aim of 
reducing the possibility of selection bias by the surgical team since there is no blinding. 
 
It is possible that some patients who are eligible before surgery and who have signed the 
informed consent, will cease to be eligible if macroscopic signs suggestive of PAS are 
not found at laparotomy (See Appendix 2: Definition of confirmed PAS case) (that is, if 
present a false positive result of the prenatal diagnostic images), which has been described 
in up to 22.6%11 of the cases. These patients will be considered screening failures in the 
recruitment process and will be excluded from the statistical analysis. 
 
9.5.1.  Inclusion criteria:  
 
- 
Pregnant women over 18 years of age. 
- 
History of previous cesarean section and anterior placenta previa 
- 
Patients with prenatal diagnosis by ultrasound or MRI of PAS (See Appendix 
2: Definition of a suspected case of PAS), regardless of the suspected degree of 
severity of the disease. 
- 
Requirement for surgical management of placental accreta on a scheduled basis. 
- 
Patients without active vaginal bleeding in the period immediately before 
surgery (Patients entering the operating room without active bleeding). 
 
9.5.2.  Exclusion Criteria:  
- 
Women without previous living children. 
 
9.6.  Sample size: 
 
As the aim of the study is not to compare the effectiveness between interventions, a formal 
power calculation was not performed. A sample size of 60 participants. According to the 
estimated recruitment rate for each center, the following distribution is proposed: 36 
patients from Indonesia, 12 patients from Argentina and 12 patients from Colombia to 
address the feasibility objectives. 
 
 
9.7. Recruitment strategy:  
 
9.7.1. Participant selection:  
 
Women with a previous cesarean section, anterior placenta previa, signs of PAS on 
ultrasound or prenatal magnetic resonance imaging (See Appendix 2: Suspicious case of 

  
 
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PAS) and who meet the inclusion criteria will be considered as possible candidates to 
participate in the study. Patients will be identified by the medical group and evaluated for 
their eligibility at the time of hospital admission before surgery. 
Once the treating medical personnel confirm the eligibility of the patient, she will be 
provided with complete information about the study and the physical informed consent, 
the patient will have at least 48 hours to evaluate it, discuss it and decide whether or not 
she wishes to participate. 
 
Participants who voluntarily decide to take part in the study will not receive any payment 
or remuneration as a result of their participation. 
 
Some anonymized data of the women who decline their participation in the study and that 
will be used in the CONSORT report will include: 
 
Date of cesarean section. 
Ethnicity 
Number of living children 
Reason why the patient is not eligible, or if she is eligible because she declined to 
participate. 
 
Before the start of the surgical procedure, the clinical coordinator of the study will be in 
charge of revealing the surgical intervention to which the patient has been randomized to 
reduce the probability of selection bias since blinding is not possible in this study. 
 
Once the laparotomy has been performed, the surgeon will define whether or not there are 
macroscopic signs on the anterior face of the uterus that confirm the diagnosis of PAS (See 
Appendix 2, Confirmed case of PAS). The clinical diagnostic criteria reported by the 
International Federation of Gynecology and Obstetrics (FIGO) will be used17. 
 
At that time, if the diagnosis of PAS is confirmed, the randomized intervention will continue. 
If the diagnosis of PAS is not confirmed, the patient will be considered a screening failure. 
 
The entire process from the disclosure of the randomization, the confirmation or exclusion of 
PAS and the performance of the randomized intervention will be supervised by the study 
coordinator in each hospital. 
 
Additionally, as a quality control, all surgery will be recorded on video and photos. With 
special emphasis on intraoperative findings after laparotomy that confirm or rule out the 
diagnosis of PAS and define the continuity of the patient in the study, or the exclusion of it 
(in case PAS is ruled out). The photographic and video recording of the findings during 
laparotomy should account for the presence of the clinical criteria for PAS endorsed by 
FIGO17 (See Appendix 10). 

  
 
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Additionally, a photo and video record will be taken of the prenatal ultrasound that suggests 
a diagnosis of PAS (according to the medical criteria of the investigator), as well as photos 
of the histological study that confirm or rule out the diagnosis of PAS.  Those patients who 
meet all the inclusion criteria and all the exclusion criteria are discarded will finally be chosen 
for the study (See Appendix 2: Inclusion / Exclusion Form). Each center will be responsible 
for completing the information of all the participants who were not entered into the study, 
recording the reasons for their NOT inclusion (See Appendix 3: Summary Screening). 
 
 
9.8.  General flowchart of study 
 
 
 
 
 
 
 
 
 

  
 
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9.9. Randomization flowchart 
 
 
 
9.10. Procedures flowchart 
 
Visit 
number 
V1 
V2 
V3 
V4 
V5 
Vn 
Day  
D0 
D1 
Hasta 72h 
Postoperatori
as 
D7 a  D12 
Postoperator
io 
D42 
Postoperator
io 
Visitas no 
programad
as 
Name of the 
visit 
Selecció
n 
Aleatorizaci
ón 
Seguimiento 
1 
Seguimiento 
2 
Fin de 
Seguimiento  
Seguimient
o N 
Activity  
 
 
 
 
 
 
Hospital 
admission 
X 
 
 
 
 
X 
Inclusion and 
exclusion 
criteria 
X 
X 
 
 
 
 
Assignment 
of 
consecutive 
number 
(Screening) 
X 
 
 
 
 
 
Informed 
consent 
X 
 
 
 
 
 
Demographic 
data 
X 
X 
 
 
 
 

  
 
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Obstetrics 
and 
gynecology 
history 
X 
X 
 
 
 
 
Short 
Physical 
Examination 
(Height and 
weight) 
 
X 
 
 
 
 
Laparotomy / 
Randomizati
on 
 
X 
 
 
 
 
Hydrostatic 
balloon 
uterine 
tamponade 
 
X 
X 
 
 
 
Characteristi
cs of the 
surgical 
procedure 
 
X 
 
 
 
 
Newborn: 
vital status 
and weight 
 
X 
X 
 
 
 
Type of 
postoperative 
hospitalizatio
n 
 
 
X 
 
 
 
Complication 
of surgery 
 
 
X 
X 
X 
X 
ICU 
admission 
 
 
X 
X 
X 
X 
Surgical 
reinterventio
n 
 
 
X 
X 
X 
X 
ICU 
discharge 
 
 
X 
X 
X 
X 
Evaluation 
Near Miss 
Criteria 
 
 
X 
X 
X 
X 
Blood 
component 
transfusion 
 
 
X 
X 
X 
X 
Arterial 
thrombosis 
associated 
with vascular 
intervention 
 
 
X 
X 
X 
X 
Ileum 
 
 
X 
 
 
 
Supra fascial 
hematoma 
 
 
X 
 
 
 
Surgical 
wound 
infection 
 
 
 
X 
X 
X 

  
 
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Clavien 
Dindo Scale 
 
 
X 
X 
X 
X 
Hospital 
discharge 
 
 
 
X 
X 
X 
Adverse 
Events 
 
X 
X 
X 
X 
X 
Telephone 
contact 
(Telemedicin
e) 
 
 
 
 
X 
 
 
9.11. Operative aspects: 
 
Eligible women will receive complete information about the study. If they agree to 
participate in it, they will sign the informed consent for both interventions: hysterectomy 
and partial myometrial resection. The final modality of intervention will be decided at 
randomization prior to the start of the surgical procedure. 
 
The patients will undergo laparotomy with adequate anesthesia, the anesthesia method 
will be decided based on the pre-anesthetic evaluation and the mother's choice. During 
laparotomy, the clinical signs and the FIGO classification for PAS will be recorded17: 
Once the abdomen is surgically entered, the anterior aspect of the uterine segment is 
observed in detail (it is likely that a vesicouterine dissection will be required) and the 
diagnosis of PAS is confirmed ( See Appendix 2, Definition of confirmed case of PAS). 
 
If the diagnosis of PAS is ruled out (If the clinical criteria for PAS proposed by FIGO 
[Appendix 2] are not present), the patient is excluded from the study and subsequent 
surgical management will be defined by the treating surgical group. 
 
If the diagnosis of PAS is confirmed by observing the clinical criteria endorsed by FIGO 
(Appendix 2), the patient's participation in the study is confirmed and the surgical 
procedure defined by randomization is continued, that is, one of the two arms of the study: 
 
Primary hysterectomy: An incision will be made above the level of the placenta, 
delivering the newborn. Uterotonics will be administered, and spontaneous delivery of 
the placenta will be awaited using gentle traction. The absence of spontaneous separation 
of the placenta will confirm the diagnosis of PAS, the patient will undergo hysterectomy. 
The complete removal of the uterus will be attempted, including the cervix, the duration 
of the intervention and intraoperative blood loss will be recorded, as well as the damage 
to organs neighboring the uterus. In this arm of the study, hysterectomy will be performed 
in 100% of patients. 
 
Partial myometrial resection: The technique described by Palacios-Jaraquemada et al5. 
will be followed. Briefly, the uterus will be dissected to free it from the posterior wall of 

  
 
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the bladder to the cervix. The vesico-uterine vessels will be ligated and the parametrial 
space will be visualized. The hysterotomy will be performed in the upper segment, 
immediately above the area of invasion of the myometrium. The entire invaded 
myometrium and the entire placenta will be removed. The uterus will repair itself in one 
or two layers. Intrauterine balloon tamponade will be used if indicated. 
 
Post-operative care will be routine care according to the indication of the treating medical 
team. 
 
To consult the detailed description of the interventions (hysterectomy and partial 
resection) and the procedures for the evaluation of clinical outcomes, see the standardized 
operating plan (See Appendix 4) 
 
From the admission of the patient to the obstetric care unit until the end of the study 
follow-up process (42 days after the cesarean section), it will be evaluated whether the 
patient meets the criteria for extreme maternal morbidity (Consult the maternal morbidity 
surveillance protocol Extrema Cod: 549 of the National Institute of Health, available at: 
https://www.ins.gov.co/buscador-eventos/Paginas/Fichas-y-Protocolos.aspx) in case of 
meeting any of the inclusion criteria, the treating medical team will be in charge of filling 
out the individual notification form Cod. INS 549 for immediate reporting 
 
In the same way, in the event of the death of a participant during the study period, due 
diligence of the individual notification form will be carried out for the maternal mortality 
event, INS Code 551 by the treating medical team. 
 
9.12.  Randomization:  
 
There will be a randomization in a 1: 1 ratio in blocks of 4 and 6, stratified by each center. 
This process will be conducted by a statistician from the Fundación Valle del Lili Clinical 
Research Center independent of the research group, who will use a public access package: 
Random Allocation Software (http://www.msaghaei.com/Softwares/dnld/RA .zip) for 
that purpose.  
 
The randomization sequence will rest in the RED Cap® software. Prior to the start of the 
surgical procedure, the clinical coordinator of the study will be asked to reveal the result 
of the randomization, once the presence of PAS is confirmed (See Appendix 2, confirmed 
case of PAS), the surgery will continue towards one of the two possible options 
(hysterectomy or partial myometrial resection). Participants and researchers will be 
informed of the intervention since it is an open-label clinical experiment. 
 
 

  
 
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9.13. Blinding:  
 
This is an unblinded study as it is not possible to conceal the surgical procedure for each 
arm from the operator (Treating Physician) or from the participant. 
 
The information of each patient will be consigned in electronic formats. In these, the 
therapeutic modality will not be expressly identified, in such a way that the independent 
statistician who will perform the analysis will also, in principle, not know the group to 
which each patient was assigned. 
 
9.14. Statistical analysis plan 
Statistical analysis will be performed in accordance with the principles of intention-to-
treat analysis. Descriptive statistics will be used to summarize the feasibility results. 
According to the CONSORT guide for feasibility experiments (Eldridge et al., 016), 
efficacy tests are not recommended, because the study is not designed to detect 
differences between the types of surgery, therefore, for the clinical outcomes analyzes 
will focus primarily on descriptive analyzes using the mean (standard deviation) or 
median (interquartile range) for continuous outcomes and absolute frequencies and 
percentages for categorical outcomes. For the specific objective of the degree of 
variability of the bleeding methods, the coefficient of variation of each method within the 
surgical techniques will be calculated. STATA version 14.0 ® software will be used. 
9.15. Interim analysis:  
An interim analysis will be carried out when 10 patients have been randomized, to 
evaluate possible factors to improve in the execution of the study. This interim analysis 
will be carried out by the executing institution and the research group. 
10. Data collection, patient follow-up, study monitoring and clinical outcomes:  
10.1. Data collection:  
A CRF ("case report form") will be designed together with the systems support staff of 
Fundación Valle del Lili, the clinical history will be used as the source document, from 
which the data of interest will be obtained to be entered into the RED Cap® electronic 
platform where the variables to be studied will be recorded and the demographic data of 
the participants, obstetric history (pregnancy and parity) of previous surgeries that include 
cesarean deliveries or uterine curettage or other gynecological surgery will be collected, 
gestational age at diagnosis, gestational age at delivery, and birth outcome. Prenatal 
complications, particularly bleeding before delivery (number of episodes and quantity, 
blood transfusions) will be recorded. 
The type of surgical procedure, the type of anesthesia, the duration of the procedure, the 

  
 
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surgical details, the volume of total intra-surgical bleeding, the details of the transfusion 
of blood components and the surgical complications, transfer to the Intensive Care Unit 
(ICU), length of stay in ICU in days / hours, the WHO Near Miss criteria (Appendix 1). 
Postoperative complications and the total length of hospital stay will be recorded. 
Information will be collected about the histopathological analysis of the surgical 
specimen in relation to the confirmation of the pathology and the degree of invasion 
described in the report. 
The data collected will be stored by the executing institution and the participating 
institutions in the RED Cap® electronic platform, the main researchers of each of the 
participating centers will be in charge of collecting the information required in the 
protocol, each of them will have a profile used for the electronic entry of the information. 
 
The information collected in this study will be recorded in a way that the subjects cannot 
be identified at any time. Any change in the process must be reported to the institutional 
review board (or Institutional Review Board IRB) of the clinical research center of 
Fundación Valle del Lili by the study coordinator. 
 
This database will not have specific information on substance abuse, psychiatric 
disorders, sexually transmitted diseases, or identifier such as name or identity document 
number. 
 
Information from health records such as diagnoses, progress notes, medications used, 
procedures performed, laboratory findings, radiology, etc. will be stored. 
 
This study does not contemplate the use of any device or investigational drug, no 
specimens or biological samples will be collected from patients for this study. 
It is important to note that, in the three institutions invited to participate, the principal 
investigators currently carry out several research projects on PAS. Thus, the prospective 
collection of clinical and paraclinical variables of interest in PAS is an established habit 
in each of the surgeries for this disease. The three clinical leaders from each institution 
have successfully completed several observational projects around PAS and have 
scientific publications in indexed journals. Additionally, they agree to submit to the audit 
of each of their research groups and to centralized surveillance by the research center of 
the Fundación Valle del Lili, during the execution of this project.  
 
10.2. Follow up assessments:  
The study participants will be followed up to evaluate the primary and secondary 
outcomes and the appearance of adverse events during 4 moments: 

  
 
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10.2.1.  Intraoperative: The total intraoperative bleeding volume will be measured, type 
of anesthesia used, type of skin incision, type of uterine incision, FIGO PAS 
classification, use of interventional radiology, use of intraoperative cell saver 
(“cell saver”), duration of surgery, use of uterine tamponade with hydrostatic 
balloons, gender and weight of the newborn. 
 
10.2.2.  Immediate post-operatory time: defined as the first 48 to 72 hours after the 
intervention, in this period of time, the patient will be monitored in the obstetric 
gynecological service, where each of the secondary outcomes described will be 
evaluated: Maternal death, Presence of Near Miss criteria, frequency and volume 
of transfusion of blood components, bladder injury, ureteral injury, need for 
reoperation, admission to ICU, days of postoperative hospital stay, disseminated 
intravascular coagulation, hypovolemic shock, metabolic acidosis, urinary 
retention, femoral thrombosis , post-operative ileus, supra fascial hematoma. 
 
10.2.3.  Medical appointment between 7 and 12 days: The patient is clinically 
evaluated by outpatient consultation on-site or telemedicine with the treating 
physician who determines if any of the secondary outcomes described above have 
occurred and additionally if she has developed an infection of the surgical wound.  
 
10.2.4.  Follow-up at 42 days postpartum: the patient will be followed up by telephone 
when she reaches 42 days after the surgical intervention, where a general 
evaluation of her health will be made, and the follow-up will be terminated. 
10.3.Data quality monitoring:  
Both the executing institution and the institutions participating in the study will designate 
a person in charge of monitoring the quality of the data. In the executing institution, the 
person in charge will be Dr. Liliana Vallecilla, who will perform a data quality analysis 
of 100% of the data corresponding to the primary outcome to be evaluated and 100% for 
the secondary outcomes, in this analysis of quality, a review of the data entered into the 
system will be carried out and it will be compared with the clinical records of each 
institution, the process will be carried permanent and will be programed the first 
monitoring with each center 5 days after to first participant enrollment, the additional 
monitoring visits will be performed according to recruitment rate and presence of primary 
and secondary outcomes in participating individuals. 
The two institutions invited to participate will also receive supervision from the monitor 
of this study at Fundación Valle de Lili, who will establish frequent communication with 
the coordinators of the centers in Argentina and Indonesia. 
 
 

  
 
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10.4. Duration of the study: Taking into account the frequency of cases of this pathology 
per year, it is estimated that each executing institution will attend 1 or 2 cases of 
PAS per month, with a total duration of 24 months. 
 
10.5. Study completion: The study is considered to end for each patient 42 days after 
surgery when the last moment of follow-up is performed. The feasibility study ends 
42 days after the cesarean section of the last randomized patient  
 
10.6. Withdrawal of informed consent: The participant or their legal representative may 
voluntarily withdraw their consent to participate in the study for any reason and at 
any time. In case of withdrawal of informed consent, the usual follow-up of the 
patient will continue during the post-surgical period and the follow-up appointment 
in 7 to 12 days. The only time of the follow-up that will not be carried out will be 
the telephone control at 42 days postpartum. Once the informed consent is 
withdrawn, no further information will be collected, the information collected until 
the moment of withdrawal of consent will be used in the analyzes contemplated in 
the study. 
11.  Ethical considerations  
The study will be submitted to the evaluation of the local ethics committee for its 
approval. 
 
11.1. Risk Level (According to Resolution 8430) 
This study complies with the CIOMS declarations, international human research 
agreements such as the Helsinki declaration and the Nuremberg code, and the national 
regulations of article 11 of resolution 8430 of 1993, It is considered a study with risk 
“greater than the minimum”, since it is a study where two surgical interventions will be 
randomized. However, these interventions are part of the conventional and accepted 
therapeutic options for the management of PAS. Given the implicit risk of this study, 
informed consent will be requested from all patients prior to undergoing any intervention. 
To ensure the confidentiality of the data, the identification variables of each patient will 
be coded to prevent the traceability of the identification; no one outside the research group 
or the ethics committee will have access to the database, and no data will be published 
that would allow the identification of the participants. 
Before the start of the study, the approval of the ethics committee will be requested for 
the study protocol, the informed consent forms, and the declaration of the mother head of 
the household. 
Substantial amendments that require review by the ethics committee will not be 
implemented until the committee provides a favorable opinion for the trial. 

  
 
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Informed consents obtained from randomized patients will be notified monthly to the 
ethics committee for review. The inclusion of the first participant will be notified to the 
committee within the first 24 hours after signing the informed consent. A semiannual 
report on the progress of the study will be made or sooner if this is required 
The principal investigator will notify the ethics committee of the end of the study. If it is 
terminated prematurely, the committee will be notified explaining the reasons for the 
premature termination. 
11.2. Consent:  
According to resolution 8430 of 1993, article 14, for research on human beings, there will 
be written informed consent, by which the research subject or their legal representative 
understands and accepts their consent (Appendix 7). 
To obtain informed consent to the legal representative, the following information will be 
provided 
a) Purpose of the investigation and procedures 
b) Study inclusion criteria and time of participation 
c) Risks and benefits 
d) Confidentiality of information 
e) Payments and compensation 
Informed consent will be obtained before the participant undergoing any trial-related 
intervention. Because this study considers a vulnerable population (pregnant women) as 
the reference population, the informed consent is based on resolution 8430, article 30, 
where it is contemplated that the informed consent of the woman and her spouse must be 
obtained, prior information from the possible risks for the embryo, fetus or newborn in 
your case. If informed consent cannot be obtained from the spouse, there will be a 
statement from the mother head of the family where the study participant certifies that 
she is economically and socially responsible for her minor children ( Appendix 8). 
The principal investigator retains overall responsibility for conducting research on his 
site, this includes obtaining informed consent from participants on his site. They must 
ensure that any person to whom the responsibility of participating in the informed consent 
process is delegated is duly authorized, trained, and competent to participate in 
accordance with the ethically approved protocol, the principles of Good Clinical Practice 
(GCP), and the Declaration of Helsinki. If a delegation of consent is acceptable, details 
must be provided. 

  
 
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The participant will remain free to withdraw at any time from the trial without giving 
reasons and without jeopardizing her further treatment and will be provided with a point 
of contact where she can obtain further information about the trial. The data collected up 
to the time of withdrawal will only be used after withdrawal if the participant has 
consented to it. Any intention to use such data will be described in the consent literature. 
When a participant is required to give her consent again or a participant is required to 
provide new information, it will be the responsibility of the principal investigator to 
ensure that this is done promptly. 
The Principal Investigator at each site assumes responsibility for ensuring that all 
vulnerable participants are protected and voluntarily participate in an environment free 
from coercion or undue influence. 
Consent will include the use of anonymous images (ultrasound or MRI), photographic 
and video recording of operative findings, as well as histopathology slides for 
independent review by blind experts. 
11.3. Conflict of interests 
The researchers of this study declare that they have no conflicts of interest. 
 
12.  Report of adverse events: 
The principal investigator of each center will be responsible for managing the safety of 
each participant and identifying adverse events related or not to the study interventions. 
Adverse events should be recorded with the following information: 
 Identification of the participant in the study. 
 Time from randomization to occurrence of the event. 
 Identification of the possible causal relationship between the event and the 
surgical intervention (hysterectomy or partial myometrial resection) 
 Resolution or improvement of the adverse event. 
 
12.1.Monitoring of adverse events: 
All adverse events (AE) that occur within the first 42 days after randomization must be 
reported to the respective ethics committee following the guidelines for reporting serious 
adverse events (SAE), maintaining the confidentiality of the information. The SAE must 
be reported to the committee within the first 24 hours of the event. 
12.2.  Definition of adverse event: An Adverse Event (AE) is considered to be any 
adverse medical situation in a patient or subject of a clinical investigation who was 

  
 
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29 
 
administered a pharmaceutical product or underwent a procedure and that does not 
necessarily have a causal relationship with this treatment. . Therefore, an AE can be any 
unfavorable or unintended sign (including an abnormal laboratory finding), symptom or 
disease temporarily associated with the use of a medicinal product (research) or a certain 
intervention, whether or not it is related to it. product or intervention. 
 Events that meet the definition of EA and their expected frequencies: 
 Transfusions of more than 4 units of red blood cells (UGR):> 40% 
 Bladder injury:> 60% 
 Ureteral injury:> 30% 
 Surgical wound infection:> 30% 
 Complications related to intra-arterial balloons such as vessel thrombosis:> 30% 
 
Events that DO NOT meet the definition of EA: 
 Post-operative ileus 
 Urinary retention 
 Supra fascial hematoma 
 Postpartum hemorrhage <2.5 L 
 Expected daily fluctuations of pre-existing diseases or conditions present or 
detected at the beginning of the study that do not worsen. 
12.3. Definition of serious adverse event (SAE) 
Serious adverse event (SAE) is defined as any unfavorable occurrence that has the 
following characteristics: 
 Cause death 
 Life-threatening: “Life-threatening” corresponds to situations in which the 
participant was at risk of death at the time of the event. 
 Requires hospitalization (hospital admission for constant observation or prolongs 
existing hospitalization) 
 Causes a significant disability or alteration of a person to perform normal vital 
functions, persistent or significant disability, does not include events of minor 
significance such as common headache, nausea, vomiting, diarrhea, flu, accidental 
trauma that may interfere with normal functions of everyday life and prevent 
them, but they are not important events. 
 Congenital anomaly / birth defect in the participant's offspring. 

  
 
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 Major medical events at the discretion of the principal investigator that may 
endanger the participant. 
12.4.EA and SAE registration: 
 The investigator will review all the documentation related to the adverse event 
and verify that it is consigned in the adverse event report form (Appendix 6). 
 The investigator will determine a diagnosis based on symptoms, signs, and all 
clinical information. The diagnosis is the one that is recorded as an adverse event. 
 In the event of serious adverse events, the principal investigator will report them 
to the institutional ethics committee within the first 24 hours of detecting the 
adverse event. 
 In case of adverse events, the principal investigator will report it to the 
institutional ethics committee within the first month of detecting the adverse 
event. 
 
12.5. Assessment of AE intensity: 
The researcher will carry out an evaluation of the intensity of each AE and SAE: 
 
Grade 1 or mild: Mild symptoms that cause minimal or no interference with social 
activities and usual functions with indicated intervention. 
Grade 2 or moderate event: Moderate symptoms causing more than minimal 
interference with usual social and functional activities with indicated intervention. 
Grade 3 or serious event: Serious symptoms that cause inability to perform usual social 
and functional activities with indicated intervention or hospitalization. 
Grade 4 or life-threatening event: possibly life-threatening symptoms causing inability 
to perform basic self-care functions with indicated intervention to prevent permanent 
failure or ongoing disability or death. 
Grade 5 death related to AE. 
 
12.6. Adverse event evaluation and safety committee: 
The safety committee will be integrated by: 
 Methodologist / statistician: Diana Marcela Martínez 
 Peer evaluator: Obstetrician gynecologist specialized in Intensive Care: Dr Juan 
Manuel Burgos Luna 

  
 
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 Obstetrician gynecologist specialized in Epidemiology: Dr Natalia Catalina 
Riascos Caipe 
All independent of the group of researchers. 
They will be in charge of monitoring the occurrence of AE and the proper conduct of the 
study. 
12.7. Assessment of causality: 
The safety committee will determine the probability that the protocol caused the AE. The 
committee may change its opinion on causation based on AE tracking information. The 
criteria presented below are intended to serve as a reference: 
 Exposure: Proof that the participant was exposed to the product. 
 Temporal evaluation: Time since the intervention in relation to the moment of the 
AE onset. 
 Probable cause: Cause that most reasonably explains the occurrence of the AE 
12.8.Protection of the safety of the participants: 
As part of the management of the previously exposed medical and legal risks, Fundación 
Valle del Lili, will acquire a civil liability policy to ensure the safety of the participants 
in the event of an accident or adverse event. 
 
13. SCHEDULE: 
 
Activity / Year 
March- April 2021 
May 2021 
Agust 2021- 
September 2023 
October 2023- 
June 2023 
1. Protocol writing 
X 
 
 
 
                                              Approvals 
 
2. Presentation of the 
protocol 
X 
 
 
3. Methodological 
evaluation  
 
X 
 
 
4.  Evaluation 
by 
the 
FVL ethics committee 
X 
 
 
                                                  Execution 
 
5. Data collection 
X 
 

  
 
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6. Analysis 
of 
the 
information 
 
 
X 
                                              Socialization of Results and Reports 
 
7. Manuscript writing  
 
 
 
X 
8. Poster presentation 
 
 
 
X 
9. Manuscript 
submission  
 
 
 
X 
10. Article publication 
 
 
 
X 
 
14. BUDGET 
The two surgical options contemplated in this study are procedures performed routinely 
in participating hospitals. They are also part of the management options contemplated in 
the international PAS management guidelines. The costs of the surgery will be assumed 
by the insurers (medical insurance company) of each patient who, even before the 
execution of this project, include both surgical management options (hysterectomy and 
partial myometrial resection) among the benefits contracted with the participating 
hospitals.  
The proposed methodology does not include the addition or subtraction of any input or 
surgical procedure to the usual medical practice in hospitals, in this way the costs of care 
for hospitals will not be modified. 
The time allocated to this study by the researchers and coordinators in each participating 
hospital will be assumed by the principal investigator or the institution that in each 
country will assume the research agreement with Fundación Valle del Lili.  
 
 
 
  
 
 
 
 

  
 
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15.  VARIABLES:  
Feasibility variables 
Variable 
Definition 
Tipe of variable 
Operative leve 
Outcome 
measure  
Women who 
participated in the 
study 
Number of women 
who agreed to 
participate in the 
study 
Continuous 
quantitative 
Number 
Frequency and 
percentages 
Screening Failure 
Number of women 
who had suspected 
PAS by ultrasound 
or magnetic 
resonance, agreed to 
participate in the 
study, but 
intraoperatively the 
diagnosis of PAS 
was ruled out (False 
positive) 
Continuous 
quantitative 
Number 
Frequency and 
percentages 
Number of 
subjects 
randomized per 
month 
Number of women 
who agreed to 
participate in the 
study and were 
randomized to one 
of the arms of the 
study 
Continuous 
quantitative 
Number 
Frequency and 
percentages 
Randomization 
arm 
Arm to which the 
patient was 
assigned 
Qualitative 
nominal 
1.Hysterectomy 
2. Partial 
myometrial 
resection 
Frequency and 
percentages 
Surgical 
intervention 
performed 
Surgical 
intervention 
performed to each 
participant 
Qualitative 
nominal 
1.Hysterectomy 
2. Partial 
myometrial 
resection 
Frequency and 
percentages 
Patients 
completing follow-
up 
Number of patients 
who complete 
follow-up up to 42 
days postpartum 
Continuous 
quantitative 
 
Number 
Frequency and 
percentages 
 
 
Sociodemographic characteristics 
Variable 
Definition 
Tipe of variable 
Operative leve 
Outcome measure  
Maternal age 
Age of the patient at 
the time of care for 
the obstetric event 
Continuous 
quantitative 
Number (Years) 
Tendency and 
dispersion 
Weight 
Weight in Kg 
Continuous 
quantitative 
Number (Kg) 
Tendency and 
dispersion 
Height 
Height in cm 
Continuous 
quantitative 
Number (cm) 
Tendency and 
dispersion 
Body mass index 
Patient kilograms 
over square meters 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Gravity 
Number of 
pregnancies the 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 

  
 
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patient has had, 
counting the current 
Parity 
Number of previous 
deliveries of the 
patient at the time of 
care 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Previous Abortions 
Number of abortions 
the patient has had at 
the time of care 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Previous caesarean 
sections 
Number of previous 
cesarean sections the 
patient has had at the 
time of care 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Previous Dilation 
& curettage 
Number of previous 
curettage 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Previous 
myomectomies 
Number of previous 
myomectomies 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
 
 
 
Characteristics of the current pregnancy 
Variable 
Definition 
Tipe of variable 
Operative leve 
Outcome measure  
Gestational age at 
the time of 
diagnosis of PAS 
Gestational age at 
the time of diagnosis 
of PAS 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Diagnostic method 
of PAS 
The diagnosis of 
PAS was made by 
ultrasound or MRI 
Qualitative 
nominal 
1.Ultrasound 
2.Magnetic 
Resonance 
3. Ultrasound and 
Magnetic Resonance 
Frequency and 
percentages 
Vaginal bleeding 
during the first 
trimester of 
pregnancy 
 
Presence of vaginal 
bleeding during the 
first trimester of 
pregnancy 
 
Qualitative 
nominal 
 
0.NO 
1. YES 
 
Frequency and 
percentages 
Presence of 
antepartum 
hemorrhage 
Did the patient have 
vaginal bleeding 
before delivery? 
Qualitative 
nominal 
0.NO 
1. YES 
Frequency and 
percentages 
Antepartum 
hemorrhage 
volume 
Volume of bleeding 
before delivery 
Continuous 
quantitative 
Number (Milliliters) 
Tendency and 
dispersion 
Diagnosis of 
hypertensive 
disorder 
The patient has a 
diagnosis of some 
type of hypertensive 
disorder during 
pregnancy 
Qualitative 
nominal 
0.NO 
1. YES 
Frequency and 
percentages 
Diagnosis of 
Gestational 
Diabetes 
The patient is 
diagnosed with 
diabetes during 
pregnancy 
Qualitative 
nominal 
0.NO 
1. YES 
Frequency and 
percentages 
 
 
Surgical features 

  
 
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Variable 
Definition 
Tipe of 
variable 
Operative leve 
Outcome 
measure  
Screening failure 
Screening failure for 
false positive 
diagnosis of PAS 
Qualitative 
nominal 
0.NO 
1. YES 
Frequency and 
percentages 
Gestational age at 
birth 
Semanas y días a los 
cuales se dio el 
nacimiento 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Type of anesthesia 
used in the surgical 
procedure 
Type of anesthesia 
used during the 
surgical 
management of PAS 
Qualitative 
nominal 
1. Neuraxial 
2.General 
3. Neuraxial with 
conversion to general 
  
Frequency and 
percentages  
Type of skin incision 
What type of skin 
incision is made 
during the surgical 
management of PAS 
 
Qualitative 
nominal 
 
1. Vertical 
2. transverse  
 
Frequency and 
percentages 
Type of uterine 
incision 
What type of uterine 
incision is made 
during the surgical 
management of PAS 
Qualitative 
nominal 
1. Upper uterine segment 
2. Lower uterine segment 
3. Fundic 
Frequency and 
percentages 
FIGO PAS 
Classification 
Categories 
described by FIGO 
of the EAP 
Qualitative 
ordinal 
0. Grade 1 
1. Grade 2 
2. Grade 3A 
3. Grade 3B 
4. Grade 3C 
Frequency and 
percentages 
Topographic 
classification of the 
PAS 
Topographic 
classification of 
placental accreta 
Qualitative 
nominal 
1.S1 
2. S2 
Frequency and 
percentages 
Classification 
according to Palacios 
Jaraquemada 
Classification into 4 
groups described by 
Jaraquemada 
palacios in 2020 
Qualitative 
ordinal 
1. 
Tipe 1 
2. 
Tipe 2 
3. 
Tipe 3 
4. 
Tipe 4 
 
Frequency and 
percentages 
Use of vascular 
interventions 
What type of 
vascular 
intervention was 
used during the 
surgical 
management of PAS 
Qualitative 
nominal 
1.None 
2. Ligation of internal iliac arteries 
3. Endovascular occlusion of the 
internal or common iliac arteries 
(balloons) 
4.Clamping or ligation of the aorta 
5. Aortic endovascular occlusion 
(Balloon) 
6. Manual compression of the aorta 
Frequency and 
percentages 
Use of cell saver 
Cell saver was 
used during the 
surgical 
management of 
PAS 
Qualitative 
nominal 
0.NO 
1. YES 
Frequency and 
percentages 
start surgery hour 
Start surgery hour 
NA 
Hours and minutes 
 
End surgery hour 
End surgery hour 
NA 
Hours and minutes 
 
Duration of surgery 
Duration of the 
surgical procedure 
in min 
Qualitative 
nominal 
Number 
Tendency and 
dispersion 
Hystological 
confirmation of PAS 
Hystopathology 
reports a 
excluyent or 
confirmative 
diagnosis of PAS 
Qualitative 
nominal 
0. NO 
1. YES 
2. NON AVAILABLE 
HYSTOPATHOLOGY 
Frequency and 
percentages 

  
 
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PAS invasión degree 
related with 
hystopathology 
Most high degree 
of PAS according 
hystopathology  
Qualitative 
nominal 
0. Accreta 
1. Inccreta 
2. Percreta 
Frequency and 
percentages 
 
 
Clinical outcomes 
Variable 
Definition 
Tipe of 
variable 
Operative leve 
Outcome 
measure  
Intra-surgical 
bleeding volumen for 
pads stimation 
Total blood loss 
during the 
procedure for pads 
calculation 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Intra-surgical 
bleeding volumen for 
suction stimation 
Total blood loss 
during the 
procedure for 
suction calculation 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Intra-surgical 
bleeding volumen for 
Reolecting bag 
stimation 
Total blood loss 
during the 
procedure for 
recollecting bag 
calculation 
Continuous 
quantitative 
Number 
Tendency and 
dispersión 
 
Intra-surgical 
bleeding volumen  
Total blood loss 
during the 
procedure 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Hospital admission 
date 
Hospital admission 
patient date 
NA 
Day/month/year 
NA 
Hospital discharge 
date 
Hospital discharge 
patient date 
NA 
Day/month/year 
NA 
Numbers of day in-
hospital 
Total numbers of 
day in-hospital 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Numbers of day of 
postoperative stay at 
hospital 
Total numbers of 
day of 
postoperative stay 
at hospital 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Admission to intensive 
care unit (ICU) 
related whit PAS 
The patient was 
admitted to the 
intensive care unit 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
ICU admission date 
related whit PAS 
ICU admission 
date 
NA 
Day/month/year 
NA 
ICU discharge date 
related whit PAS 
ICU discharge date 
NA 
Day/month/year 
NA 
Number of days of 
ICU stay related whit 
PAS 
Number of days of 
post-operative stay 
in ICU 
Qualitative 
nominal 
Número (días) 
Tendency and 
dispersion 
Presence of at least 1 
Near Miss criterion 
The patient meets 
the WHO Near 
Miss criteria 
(Appendix 1) 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Blood component 
transfusion 
Was the patient 
transfused with any 
blood components? 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 

  
 
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Number of Units of 
red blood cells 
transfused 
Number of Units 
of Red Blood Cells 
transfused 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Number of Units of 
fresh plasma 
transfused 
Number of Units 
of fresh plasma 
transfused 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Number of units of 
platelets transfused 
Number of units of 
platelets transfused 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Number of 
Cryoprecipitate Units 
transfused 
Number of 
Cryoprecipitate 
Units transfused 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
Administration of 
lyophilized fibrinogen 
Was the patient 
given lyophilized 
fibrinogen? 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Use of uterine 
tamponade with 
hydrostatic balloons 
Use of hydrostatic 
balloons for uterine 
tamponade 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Bladder injury 
The patient 
presented bladder 
injury during the 
surgical 
management of 
PAS 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Ureteral injury 
The patient 
presented ureteral 
injury during the 
surgical 
management of 
PAS 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Intestinal injury 
The patient 
presented intestinal 
injury during the 
surgical 
management of 
PAS 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Need for surgical 
reintervention 
The patient needed 
surgical 
reintervention 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Arterial thrombosis 
related whit vascular 
interventions 
The patient 
presented arterial 
thrombosis during 
the postoperative 
period 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Post operative ileus 
The patient 
presented ileus 
during the 
postoperative 
period 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Supra fascial 
hematoma 
The patient 
presented a supra-
fascial hematoma 
in the post-surgical 
period. 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Surgical wound 
infection 
The patient had a 
surgical wound 
infection in the 30 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 

  
 
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days after the 
procedure 
Maternal death 
Maternal death of 
patient during 
study period 
Qualitative 
nominal 
0. NO 
1. YES 
 
Frequency and 
percentages 
Clavin Dindo 
complications 
classification 
Complications 
classification 
according Clavin 
Dindo 
Qualitative 
nominal 
0. Grade  I 
1. Grade  II 
2. Grade IIIa 
3. Grade IIIb 
4. Grade IVa 
5. Grade IVb 
6. Grade V 
 
Frequency and 
percentages 
Newborn status 
El recien nacido 
tenía algún signo 
de vida al 
momento del 
nacimiento 
Qualitative 
nominal 
0. live 
1. Dead 
Frequency and 
percentages 
Newborn weight 
Newborn weight in 
grams 
Continuous 
quantitative 
Number 
Tendency and 
dispersion 
 
16. TABLES: 
 
Table 1: Sociodemographic characteristics 
 
 
Total, n=60 
Group 1: 
Hysterectomy 
Group 2: partial 
myometrial 
resection 
Maternal age 
(Median IQR)  
 
 
 
Body mass index  
(Median IQR) 
 
 
 
Gravity  
(Median IQR) 
 
 
 
Parity  
(Median IQR) 
 
 
 
Previous abortions (Median 
IQR) 
 
 
 
Number of previous cesarean 
sections (Median IQR) 
 
 
 
Number of previous curettage 
 
 
 
Number of previous 
myomectomies 
 
 
 
 
Tabla 2: Characteristics of the current pregnancy 

  
 
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Total, n=60 
Group 1: 
Hysterectomy 
Group 2: partial 
myometrial 
resection 
Gestational age at diagnosis of PAS 
(Median IQR) 
 
 
 
Diagnostic method of PAS 
 
 
 
Ultrasound % 
 
 
 
Magnetic Resonance % 
 
 
 
Ultrasound and Magnetic resonance % 
 
 
 
Presence of vaginal bleeding in the 
1st trimester of pregnancy  % 
 
 
 
Presence of antepartum hemorrhage 
% 
 
 
 
Antepartum hemorrhage volume 
(Median IQR) 
 
 
 
Diagnosis of gestational diabetes  % 
 
 
 
Diagnosis of hypertensive disorder of 
pregnancy %  
 
 
 
 
Tabla 3: Características del nacimiento  
 
Total, n=60 
Group 1: 
Hysterectomy 
Group 2: partial 
myometrial 
resection 
Gestational age at birth 
(Median IQR) 
 
 
 
Type of anesthesia used in the 
procedure % 
 
 
 
Neuraxial 
 
 
 
General  
 
 
 
Neuraxial with conversion to 
general  
 
 
 
Type of skin incision 
 
 
 
Transverse% 
 
 
 
Vertical % 
 
 
 
Type of uterine incision 
 
 
 
Upper segment 
 
 
 
Lower segment 
 
 
 
Fundic 
 
 
 
FIGO Classification for PAS 
 
 
 
Grade 1  
 
 
 
Grade 2 
 
 
 
Grade 3 A 
 
 
 
Grade 3B 
 
 
 
Grade 3C 
 
 
 
Topographic classification of 
PAS 
 
 
 
S1 % 
 
 
 
S2% 
 
 
 

  
 
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Classification according to 
Palacios Jaraquemada 
 
 
 
Type 1 
 
 
 
Type 2 
 
 
 
Type 3 
 
 
 
Type 4 
 
 
 
Use of vascular interventions 
 
 
 
Use of cell saver 
 
 
 
Duration of surgery 
 
 
 
PAS confirmation for 
hystopathology 
 
 
 
Ivasion grade of PAS for 
hystopathology 
 
 
 
 
 
 
Tabla 4: Clinical outcomes 
 
 
Total, n=60 
Group 1: 
Hysterectomy 
Group 2: partial 
myometrial 
resection 
Total volume of intra-surgical 
bleeding 
 
 
 
Admission to ICU % 
 
 
 
Number of days of ICU stay (Median 
IQR) 
 
 
 
Patient meets Near Miss criteria% 
 
 
 
Blood component transfusion% % 
 
 
 
RBCU transfused (Median RIC) 
 
 
 
FPU  transfused  (Median RIC)  
 
 
 
CPU transfused (Median RIC) 
 
 
 
Fibrinogen administration % 
 
 
 
Use of hydrostatic plugging with 
balloons % 
 
 
 
Bladder Injury % 
 
 
 
Ureteral Injury % 
 
 
 
Intestinal injury % 
 
 
 
Need for surgical reintervention % 
 
 
 
Arterial thrombosis % 
 
 
 
Post operative ileus % 
 
 
 
Supra fascial hematoma % 
 
 
 
Surgical wound infection % 
 
 
 
Surgical complications according 
Clavin Dindo classification 
 
 
 
Newborn status 
 
 
 
 Newborn Weight 
 
 
 
 
 

  
 
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Table 5: Coefficient of variation (%CV) of bleeding measures methods 
 
Bleeding 
measures 
methods 
Hysterectomy 
Partial myometrial resection
Intra-surgical 
bleeding 
volumen for pads stimation 
%CV 
%CV 
Intra-surgical 
bleeding 
volumen for suction stimation 
%CV 
%CV 
Intra-surgical 
bleeding 
volumen for Reolecting bag 
stimation 
%CV 
%CV 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
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17. REFERENCIAS:  
 
1. Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA, et al. 
Maternal morbidity associated with multiple repeat cesarean deliveries. Obstet 
Gynecol. 2006 Jun;107(6):1226-32. 
2. D'Antonio F, Iacovella C, Bhide A. Prenatal identification of invasive 
placentation using ultrasound: systematic review and meta-analysis. Ultrasound 
in Obstetrics & Gynecology. 2013 NOV 2013;42(5):509-17. 
3. Jauniaux E, Bhide A. Prenatal ultrasound diagnosis and outcome of placenta 
previa accreta after cesarean delivery: a systematic review and meta-analysis. 
American journal of obstetrics and gynecology. 2017 Jul;217(1):27-36. 
4. Fitzpatrick KE, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M. The 
management and outcomes of placenta accreta, increta, and percreta in the UK: a 
population-based descriptive study. BJOG. 2014 Jan;121(1):62-70; discussion -1. 
5. Nieto AJ, Echavarría MP, Carvajal JA, et al. Placenta accreta: importance of a 
multidisciplinary approach in the Colombian hospital setting. J Matern Fetal 
Neonatal Med. 2020;33(8):1321-1329. doi:10.1080/14767058.2018.1517328 
6. Collins SL, Alemdar B, van Beekhuizen HJ, Bertholdt C, Braun T, Calda P, et al. 
Evidence-based guidelines for the management of abnormally invasive placenta: 
recommendations from the International Society for Abnormally Invasive 
Placenta. American journal of obstetrics and gynecology. 2019 Jun;220(6):511-
26. 
7. Palacios-Jaraquemada JM, Fiorillo A, Hamer J, Martinez M, Bruno C. Placenta 
accreta spectrum: a hysterectomy can be prevented in almost 80% of cases using 
a resective-reconstructive technique. The journal of maternal-fetal & neonatal 
medicine : the official journal of the European Association of Perinatal Medicine, 
the Federation of Asia and Oceania Perinatal Societies, the International Society 
of Perinatal Obstet. 2020 Jan 26:1-8. 
8. Allen L, Jauniaux E, Hobson S, Papillon-Smith J, Belfort MA; FIGO Placenta 
Accreta Diagnosis and Management Expert Consensus Panel. FIGO consensus 
guidelines on placenta accreta spectrum disorders: Nonconservative surgical 
management. Int 
J 
Gynaecol 
Obstet. 
2018;140(3):281-290. 
doi:10.1002/ijgo.12409 

  
 
RCT-PAS Version 3.0 of 20th september 2021 - Amendment 2.0 
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9. Palacios J. Tratamiento conservador uterino en trastornos adherenciales de la 
placenta: acretismo y percretismo placentario. Rev Chil Obstet Ginecol 
1998;63:363-369 
10. Sentilhes L, Kayem G, Chandraharan E, Palacios-Jaraquemada J, Jauniaux E; 
FIGO Placenta Accreta Diagnosis and Management Expert Consensus Panel. 
FIGO consensus guidelines on placenta accreta spectrum disorders: Conservative 
management. Int 
J 
Gynaecol 
Obstet. 
2018;140(3):291-298. 
doi:10.1002/ijgo.12410 
11. Nieto-Calvache AJ, López-Girón MC, Messa-Bryon A, et al. Urinary tract injuries 
during treatment of patients with morbidly adherent placenta [published online 
ahead of print, 2019 Oct 21]. J Matern Fetal Neonatal Med. 2019;1-7. 
doi:10.1080/14767058.2019.1678135 
12. Nieto-Calvache AJ, Vergara-Galliadi LM, Rodríguez F, et al. A multi-disciplinary 
approach and implementation of a specialized hemorrhage control team improves 
outcomes for placenta accreta spectrum [published online ahead of print, 2021 Jan 
25]. J Trauma Acute Care Surg. 2021;10.1097/TA.0000000000003090. 
doi:10.1097/TA.0000000000003090 
13. Nieto-Calvache AJ, López-Girón MC, Quintero-Santacruz M, et al. A systematic 
multidisciplinary initiative may reduce the need for blood products in patients 
with abnormally invasive placenta [published online ahead of print, 2020 Feb 
23]. J 
Matern 
Fetal 
Neonatal 
Med. 
2020;1-7. 
doi:10.1080/14767058.2020.1731460 
14. Nieto-Calvache AJ, Zambrano MA, Herrera NA, et al. Resective-reconstructive 
treatment of abnormally invasive placenta: Inter Institutional Collaboration by 
telemedicine (eHealth). J Matern Fetal Neonatal Med. 2021;34(5):765-773. 
doi:10.1080/14767058.2019.1615877 
15. Teixidor Viñas M, Belli AM, Arulkumaran S, Chandraharan E. Prevention of 
postpartum hemorrhage and hysterectomy in patients with morbidly adherent 
placenta: a cohort study comparing outcomes before and after introduction of the 
Triple-P 
procedure. Ultrasound 
Obstet 
Gynecol. 
2015;46(3):350-355. 
doi:10.1002/uog.14728 

  
 
RCT-PAS Version 3.0 of 20th september 2021 - Amendment 2.0 
44 
 
16. Pinas Carrillo A, Chandraharan E. Placenta accreta spectrum: Risk factors, 
diagnosis and management with special reference to the Triple P procedure. 
Womens Health (Lond). 2019 Jan-Dec;15:1745506519878081. 
17. Jauniaux E, Ayres-de-Campos D, Langhoff-Roos J, et al. FIGO classification for 
the clinical diagnosis of placenta accreta spectrum disorders,. Int J Gynecol 
Obstet. 2019;146(1):20–4. 
18. Jauniaux E, Bhide A, Kennedy A, et al. FIGO consensus guidelines on placenta 
accreta spectrum disorders: Prenatal diagnosis and screening. Int J Gynaecol 
Obstet. 2018;140(3):274-280. doi:10.1002/ijgo.12408 
19. Jha P, Pōder L, Bourgioti C, et al. Society of Abdominal Radiology (SAR) and 
European Society of Urogenital Radiology (ESUR) joint consensus statement for 
MR 
imaging 
of 
placenta 
accreta 
spectrum 
disorders. Eur 
Radiol. 
2020;30(5):2604-2615. doi:10.1007/s00330-019-06617-7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
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18. APPENDIX  
Appendix 1: Near Miss Criteria 
Clinical criteria 
Acute cyanosis 
Gasping 
Respiratory rate >40 or <6/min 
Shock 
Oliguria non-responsive to fluids or 
diuretics 
Clotting failure 
 
Loss of consciousness lasting  12 
hours 
Loss of consciousness AND absence 
of pulse/heart beat 
Stroke 
Uncontrollable fit/total paralysis 
Jaundice in the presence of pre-
eclampsia 
Laboratory-based criteria 
Oxygen saturation <90% for  60 
minutes 
pH <7.1 
PaO2/FiO2 <200 mmHg  
Lactate >5 mmol/l 
Creatinine  300 mmol/l or  3.5 
mg/dl  
 
Acute thrombocytopenia (<50 000 
platelets) 
Bilirubin>100 mmol/l or > 6.0 mg/dl  
Loss of consciousness AND the 
presence of glucose and ketoacids in 
urine 
Management-based criteria 
Use of continuous vasoactive drugs 
Intubation and ventilation for 60 
minutes not related to anaesthesia 
Hysterectomy following infection or 
haemorrhage  
 
Dialysis for acute renal failure 
Transfusion of 5 units red cell 
transfusion 
Cardio-pulmonary 
resuscitation (CPR) 
 
 
 
 
 
 
 
 

  
 
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APPENDIX 2: DEFINITION OF SUSPECT AND CONFIRMED CASE OF PAS: 
 
 
1. DEFINITION OF SUSPECT CASE OF PAS BY ULTRASOUND: 
 
Presence of any of the following ultrasound findings: 
 
1.1 Loss of the retroplacental hypoechoic line: Loss or irregularity of the hypoechoic 
plane between the myometrium and the placental border “Clear Zone”. 
 
1.2 Presence of abnormal placental lagoons: Presence of numerous lagoons including 
some long and irregular or with presence of turbulent flow. 
 
1.3 Bladder wall disruption: Loss or disruption of the bladder wall (hyper echoic band 
or line between the uterine serosa and the bladder lumen). 
1.4 Myometrial thinning: Myometrial thinning <1mm or undetectable. 
 
1.5 Placental bulge: Deviation of the serosa from the expected plane, caused by an 
abnormal bulge of placental tissue to neighboring organs, typically the bladder. 
The uterine serosa appears intact, but its contour is irregular. 
 
1.6 Focal exophytic mass: Placental tissue that surpasses the uterine serosa and 
extends beyond it, often seen within the full bladder. 
 
1.7 Uterus-vesical hypervascularization: large amount of Doppler signal between the 
myometrium and the posterior bladder wall, this sign probably indicates 
numerous tortuous vessels in this region. 
 
1.8 Subplacental hypervascularization: large amount of Doppler signal in the 
placental bed. 
 
1.9 Bridging vessels: vessels that apparently extend from the placenta and cross the 
myometrium and beyond the serosa to the bladder or other organs. 
 
1.10 
Vessels that feed the placental lagoons: vessels with high flow velocity 
that feed the placental lagoons causing turbulence at their entrance. 
 
1.11 
3D intraplacental hypervascularization: abnormal placental vessels, with 
tortuous courses and various gauges. 
 
 
 
 
 
 
 
 
 

  
 
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2. DEFINITION OF SUSPECT CASE OF PAS BY MAGNETIC 
RESONANCE: 
 
Presence of any of the following ultrasound findings: 
 
2.1 Hypointense bands in T2: One or more areas of hypo intensity in T2, usually with a 
linear configuration and in contact with the maternal surface of the placenta. 
2.2 Placental bulging: Deviation of the uterine serosa from the expected plane, caused 
by abnormal bulging of placental tissue to adjacent organs. 
2.3 Loss of the hypointense interface in T2: loss of the dark line behind the placental 
bed in T2 images. 
2.4 Myometrial thinning: Thinning of the myometrium that covers the placenta less than 
1mm or even invisible. 
2.5 Bladder wall disruption: Hypointense bladder wall irregularity or disruption, which 
may be accompanied by blood products in the bladder lumen. 
2.6 Focal exophytic mass: Placental tissue that surpasses the uterine serosa and extends 
beyond it, frequently seen within the full bladder and lateral to the parametrium. 
2.7 Abnormal vascularization of the placental bed: prominent vessels in the placental 
bed with disruption of the uteroplacental interface, can extend to the myometrium to a 
variable degree, reaching the uterine serosa and can be accompanied by extensive 
neovascularization around the bladder, uterus and the vagina. 
2.8 Placental heterogeneity: Heterogeneous signals in the placenta that can be seen on 
T1 and T2. 
2.9 Asymmetric thinning of the placenta: Part of the placenta, the portion that is 
involved with PAS and usually the part that covers the internal cervical os (in cases of 
placenta previa) are asymmetrically thinned compared to the rest of the placental tissue . 
2.10 Placental ischemic infarction: In the acute phase, areas of hyperintensity in T2 and 
hypo intensity in T1 are present, areas of placental asymmetry are described in chronic 
infarcts. 
2.11 Abnormal intraplacental vascularization: Abnormal, tortuous and elongated vessels 
in T2 deep in the placenta. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
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3. DEFINITION OF PAS CONFIRMED CASE: 
 
Confirmed case in Placenta Acreta laparotomy: The patient meets any of the 
following criteria: 
 
- No placental separation with the administration of oxytocin and controlled cord traction. 
- Attempts to remove the placenta result in heavy bleeding from the placental bed. 
- Macroscopically, the uterus does not show an obvious placental bulge, no placental 
tissue is seen invading the surface of the uterus, and there is minimal or no 
neovascularization. 
 
Confirmed case in laparotomy of Placenta increta: The patient meets any of the 
following criteria: 
- Abnormal macroscopic findings in the placental bed, bluish or purplish color, presence 
of placental bulge. 
- Increased Hypervascularization (Multiple vessels run parallel craniocaudal in the uterine 
serosa) 
- No placental tissue is observed invading through the uterine serosa. 
- Cord traction results in outward uterine traction without achieving placental separation. 
 
Confirmed case in Placenta Percreta laparotomy: The patient meets any of the 
following criteria: 
 
Placenta percreta grade 3A: Limited to the serosa: 
- Abnormal macroscopic findings on the surface of the uterine serosa, the placental tissue 
invades through the surface of the uterus. 
- It does not invade any organs, including the posterior bladder wall (there is a clear 
surgical plane between the uterus and the bladder) 
 
Placenta percreta grade 3B: With invasion of the bladder wall: 
- There are placental vessels that invade the bladder surface but not other organs. 
- A clear plane between the bladder and the uterus cannot be identified 
 
Placenta percreta grade 3C: With invasion of other pelvic organs: 
- Placental vessels invade the round ligament, vaginal wall, lateral pelvic walls, or other 
pelvic organ (with or without invasion of the bladder) 
 
 
 
 
 
 
 

  
 
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APPENDIX 3 
 
Inclusion and exclusion format 
Institution: _____________________ 
Clinic history: _________________ 
Screening number:  
 
Inclusion and exclusion  criteria__ __ 
 
 
Inclusion criteria 
Yes 
No 
1 
Pregnant woman over 18 years of age 
 
 
2 
History of previous cesarean section and previous placenta 
previa 
 
 
3 
Prenatal ultrasound or magnetic resonance diagnosis of PAS. 
(Appendix 2, Suspected case of PAS) regardless of the 
suspected degree of severity of the disease. 
 
 
4 
Requirement for surgical management of placental accreta on a 
scheduled basis. 
 
 
5 
Patients without active vaginal bleeding in the period 
immediately prior to surgery (Patients entering the operating 
room without active bleeding). 
 
 
 
 
 
Exclusion criteria 
Si 
No 
1 
Woman without children or newborns 
 
 
 
Elegible patient 
Si 
No 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
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Appendix 4 
Screening summary 
Institution: _________________ 
 
 
Sitio 01-FVL- SCREENING SUMMARY_ RCT-PAS Study 
Identification 
Partipation 
Not 
participating 
causes 
(number 
according to 
list) 
Date Age Name 
ID 
If 
Patient 
is 
elegible 
If 
Patient 
is not 
elegible 
 
 
 
 
Asigned 
numer 
(Group 
186) 
Asigned 
numer 
(Group 
189) 
1  
 
 
 
 
 
 
2  
 
 
 
 
 
 
3  
 
 
 
 
 
 
4  
 
 
 
 
 
 
5  
 
 
 
 
 
 
6  
 
 
 
 
 
 
7  
 
 
 
 
 
 
8  
 
 
 
 
 
 
 
Not partipating causes 
1 
Some exclusion criteria 
2 
Denial of consent 
 
 
 
 
 
 
 
 
 
 
 

  
 
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APPENDIX 5. STANDARDIZED OPERATIONAL PLAN 
All study participants will have specific roles listed below. 
Principal investigators at each center: 
- Albaro José Nieto Calvache. Fundación Valle del Lili (Cali, Colombia) 
- Rozi Aditya Aryananda. Dr. Soetomo Academic General Hospital, Universitas 
Airlangga, (Surabaya, Indonesia) 
- José Miguel Palacios Jaraquemada. CEMIC University Hospital (Buenos Aires, 
Argentina) 
Roles of the Principal Investigators: 
1. Design of the study protocol, construction of documents necessary to meet the 
requirements of regulatory committees at Fundación Valle de Lili and other 
participating hospitals. 
2. Identify candidate patients to participate in the study. Assess your eligibility using 
inclusion and exclusion criteria. 
3. Notify all study participants of the identification of a potentially eligible study 
subject. A virtual chat will be used on the Microsoft Teams® platform where all 
the participants will find out when each of the three participating centers identifies 
a potential subject to be included. 
4. Provide the patient with sufficient and clear information so that she can evaluate 
her potential participation in the study. 
5. Obtain informed surgical and study consent including hysterectomy and partial 
myometrial resection options. 
6. Provide the study coordinator with the informed consents collected to be stored 
as part of the confidential study documentation. 
When the first subject of the study is admitted, the principal investigator will 
provide the study coordinator with the informed consent completed within the first 
24 hours after collection, in order to report it to the research ethics committee. For 
the other participants included, the principal investigator will have up to 1 week 
to provide consent to the coordinator for them to be reported to the ethics 
committee within the first 5 days of each month 

  
 
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7. Convene the study coordinator before starting the surgical intervention to reveal 
the result of the randomization and assign one of the two possible surgical 
procedures. The intervention will depend on the randomization according to the 
sequence that resides in the Red Cap® software 
 
8. Confirm or rule out the diagnosis of PAS by observing clinical criteria during 
laparotomy: 
a. To perform laparotomy and before performing hysterotomy (opening the 
uterus), confirm the presence of clinical signs of PAS on the anterior surface 
of the uterus. The presence of the signs described by the consensus of the 
International Federation of Gynecology and Obstetrics (FIGO), described in 
Appendix 2, will be sought. Definition of confirmed case. 
b. If the presence of clinical signs of PAS is confirmed, the patient continues 
in the study and the surgical procedure previously defined by the 
randomization process will be performed. 
c. If the presence of clinical signs of PAS is ruled out, the patient is excluded 
from the study and subsequent surgical management will be defined by the 
group of treating surgeons. 
 
9. Apply the selected surgical technique in the randomization process (hysterectomy 
or partial myometrial resection) 
 
A. Total abdominal hysterectomy: An incision will be made above the level of 
the placenta, extracting the newborn. Uterotonics will be administered and 
spontaneous delivery of the placenta will be awaited using gentle traction. The 
absence of spontaneous separation of the placenta will confirm the diagnosis of 
PAS, the patient will undergo hysterectomy. The complete removal of the uterus 
will be attempted, including the cervix, the duration of the intervention and 
intraoperative blood loss will be recorded, as well as the injury to organs 
neighboring the uterus. In this arm of the study, hysterectomy will be performed 
in 100% of patients. 
 
B. Partial myometrial resection: The technique described by Palacios-
Jaraquemada et al.5 will be followed. Briefly, the uterus will be dissected to free 
it from the posterior wall of the bladder to the cervix. The vesico-uterine vessels 
will be ligated and the parametrial space will be visualized. The hysterotomy will 
be performed in the upper segment, immediately above the area of invasion of the 
myometrium. The entire invaded myometrium and the entire placenta will be 
removed. The uterus will repair itself in one or two layers. Intrauterine balloon 
tamponade will be used if indicated 
 

  
 
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10. Carry out the prospective collection of all clinical variables during surgery. 
 
The objective measurement of the operative sac is the variable of greatest interest in 
a possible controlled clinical trial and requires special description since its correct 
measurement is basic for the analysis of results in both arms of the feasibility study 
and for the planning of a subsequent study. 
 
Objective measurement of the total intraoperative bleeding volume will be performed 
by 3 means: 
 
A. Quantification of bleeding present in intraoperative suction devices: The 
surgical team will make a visible mark on the suction devices at the time of 
initiation of surgery. The volume that the amniotic fluid will occupy in said 
devices will be taken into account. To this end, before performing the 
hysterotomy, the surgeon will notify the anesthesia and nursing team to make an 
additional mark on the suction device. Similarly, when the baby and all the 
amniotic fluid have been extracted, the surgeon will again notify the 
anesthesiology and nursing team, to make a new visible mark on the suction 
device. 
 
A record will be kept of any volume of sterile solutions used to irrigate the 
operative field (saline, lactate Ringer). This volume will be subtracted from the 
final volume count, to avoid overestimating the bleed. 
 
B. Weight 
quantification 
of 
blood-soaked 
compresses: Cleaning of the operative field with a 
compress will be preferred and not with suction 
devices. The blood-soaked compresses will be 
removed from the operative field and stored in a 
sterile container in case intraoperative cell recovery 
is required. At the end of the surgery, the weight of 
the soaked compresses will be performed and from 
the value obtained, the “dry weight” will be 
subtracted 
from 
the 
number 
of 
quantified 
compresses. The surgical team will previously know 
the weight of each compress used in your institution 
 
C. Quantification of vaginal bleeding with a calibrated collection bag: All 
participating centers will use a blood collection bag that will be placed under the 
perineum of the patient before starting the surgery. This bag has a system for 

  
 
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measuring the volume collected that will be quantified at the end of the surgery. 
The Brass V® brand collection bags will be provided by the executing institution 
and sent to the participating institutions to ensure the standardization of vaginal 
bleeding measurement. 
 
At the end of the surgery, an objective estimate of bleeding will be made by adding 
the volume of bleeding from the suction devices, that of the compresses and that 
of the vaginal bleeding collection bag. 
The three participating centers will use the same blood loss measurement protocol. 
A member of the surgical team will be assigned to perform bleeding 
measurements during surgery and immediately after the procedure. Visual 
estimation of bleeding will not be used as it has been shown that it is not a reliable 
measure since it usually underestimates losses. 
 
 
 
 
 
 
 
 
11. 
  Obtain photos and videos of the surgical procedure clearly showing the presence 
or absence of PAS. 
12. Carry out clinical follow-up during the postoperative period according to the usual 
PAS management protocols in each institution. 
13. Carry out postoperative assessment at an outpatient check-up appointment or 
telemedicine in 7 to 12 days. 
14. Make the follow-up call 42 days after surgery. 
15. Record all the study variables in the Case Report Form (CRF) designed in the Red 
Cap® virtual platform within a period between 48 hours and no more than 7 days after 
the surgery has been performed. 
15. Report identified adverse events monthly to the research ethics committee. 
16. Report serious adverse events to the research ethics committee within the first 24 
hours of the event. 

  
 
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17. Heed the recommendations of the safety and evaluation committee for adverse events. 
18. Heed the recommendations of those in charge of data quality monitoring 
19. Participate in the analysis of the information collected 
20. Participate in the writing of the article resulting from the study. 
 
Study coordinators and data quality monitors, Co- Investigators: 
 
- Stiven Ernesto Sinisterra Díaz. Fundación Valle del Lili (Cali, Colombia) 
- Nareswari Imanadha. Dr. Soetomo Academic General Hospital, Universitas Airlangga, 
(Surabaya, Indonesia) 
- Fernando Paesani. CEMIC University Hospital (Buenos Aires, Argentina) 
 
Functions of the study coordinator: 
 
1. Support the principal investigator in the design of the study protocol and the 
documentation corresponding to the study. 
2. Support the principal investigator in submitting the documentation corresponding to 
the study before the ethics committee in biomedical research within the established 
deadlines. 
3. Respond to any request by the Center for Clinical Research or the ethics committee in 
biomedical research, related to the study. 
4. Support the principal investigator in the process of recruiting and evaluating the 
eligibility of potential study participants. 
5. Provide the main researcher with the printed paperwork of the documentation that must 
be filled out during the study. 
6. Verify that the procedure for obtaining informed consent from the research subject is 
done correctly by the principal investigator. 
7. Safeguard the informed consents filled out as part of the confidential documentation of 
the study, if required. 
8. Report to the ethics committee in biomedical research the inclusion of the first 
participant in the study within the first 24 hours of their inclusion with their respective 
informed consent. 
9. Report to the ethics committee in biomedical research within the first 5 days of each 
month, the duly filled informed consents. 
10. Be attentive to the call from the principal investigator advising the start of surgery to 
reveal to the surgical team the randomized intervention assigned to the patient. This 
procedure will be performed in person when possible, if the presence in the surgery room 
of the study coordinator or the quality monitor is not possible, a video call will be used in 
which the result of the test will be transmitted to the surgical group. randomization, before 
starting surgery 

  
 
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11. Support the principal investigator in the prospective collection of study variables 
within surgery, also support the subsequent registration of it in real time (within 24 hours) 
in the CRF of the Red Cap® virtual platform within maximum 7 days after surgery. 
12. Support the principal investigator in the echography photos of prenatal diagnosis of 
PAS and the histology specimens photos collection.  
13. Receive and respond to observations made by the data quality monitor of the other 
participating institutions. 
14. Monitor the follow-up process of each of the randomized subjects in the event of any 
adverse event or serious adverse event to make their respective report to the ethics 
committee in biomedical research. (serious adverse events within the first 24 hours of 
occurrence and adverse events monthly) 
15. In the event of serious adverse events, coordinate the meetings of the adverse event 
evaluation committee with the principal investigator. 
16. In the event of any modification to the protocol or to the documentation corresponding 
to the study (Appendixes, informed consent or declaration of the mother of the head of 
the family), submit these changes in the form of an amendment to the ethics committee 
in biomedical research. 
17. Support the main researcher in the writing and submission of the article resulting from 
the study. 
18. Ensure that all study procedures are carried out in accordance with the provisions of 
the protocol and what is approved by the ethics committee in biomedical research of 
Fundación Valle del Lili. 
 
Data quality monitor functions: 
1. Weekly they will evaluate compliance with the registration of the information of the 
patients included in the CRF of the Red Cap® platform 
2. Evaluate that the information recorded for each patient included is complete and that 
there are no missing data. 
3. They will carry out a monthly review of the quality of the information collected, 
comparing the data registered in the CRF and the database, with the clinical history of the 
patients in each institution, this will be done in 100% of the data related whit primary 
outcomes and 100% of the data related whit secondary outcomes. 
4. They will report the findings found in the monitoring of the data to the study 
coordinator at the executing institution. 
5. They will provide feedback to the principal investigators on their performance in 
registering the data on the Red Cap® platform in case of finding inconsistencies in the 
data. 

  
 
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Serious adverse event evaluation and safety committee: 
Methodologist / statistician: Andrea Valencia 
Peer evaluator: Obstetrician gynecologist specialized in Intensive Care: Dr Juan Manuel 
Burgos Luna 
Obstetrician gynecologist specialized in Epidemiology: Dr Natalia Catalina Riascos 
Caipe 
All independent of the group of researchers. 
This committee is in charge of monitoring the occurrence of adverse events in study 
participants, ensuring their safety. 
1. Depending on the rate of patient recruitment, the safety committee will hold periodic 
meetings to evaluate each of the serious adverse events presented during the analysis 
period. 
2. The safety committe will be in charge of determining if the study will be stopped 
according whit the frequency of adverse events is higher than expected or if a serious 
adverse event occurs and the ethics committee will be consulted about its continuation. 
3. Evaluate the causality of serious adverse events. 
4. Evaluate the intensity of serious adverse events. 
5. The peer evaluator and the obstetrician gynecologist specializing in epidemiology will 
carry out an evaluation of the possible clinical events that will contribute to the occurrence 
of the adverse event and will generate feedback to the principal investigator on strategies 
to prevent these from occurring if they are preventable events. 
6. Issue a report of your adverse event evaluation. 
 
 
 
 
 
 

  
 
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Appendix 6: Serious adverse event reporting format 
 
 
 
 
 

  
 
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Appendix 7: Informed consent 
Appendix 8: Declaration of householder.  

  
 
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Appendix 9: Telephone contact follow-up visit day 42 format.  
Institution:  
Randomization number:  
Telephone contact date:  
 
Before to call the patient, please confirm whether the patient received vascular 
intervention to control intraoperative bleeding:   Yes ____  No ____ 
My name is: _________________ I am calling you from the Fundación Valle del Lili 
from the area of the Clinical Research Center regarding the study in which you agreed to 
participate. 
Today is her 42nd day after the surgery through which she had her baby and we want to 
follow up on her current health status. 
Miss ___________ please answer the next questions:  
Question 
Answer 
¿How are you? ¿How do you feel today? 
 
Have you had any problems or difficulties 
that 
required 
medical 
attention 
or 
consultation 
since 
your 
outpatient 
appointment? 
 
In case the patient has consulted a health 
service, ask where she went and why, and 
request a copy of the care history if 
possible.  
Send all the information to the principal 
investigator's institutional e-mail address. 
 
Regarding the wound from your surgery, 
have you had any problems with it? 
Exemplify: Is it red, warm, leaking pus or 
any fluid, confirm that your stitches have 
been removed. 
 
* If you have not received vascular 
intervention, do not ask the following 
 

  
 
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question: 
Since your last outpatient follow-up 
appointment, have you had tingling or 
numbness in your legs, skin changes such 
as bluish, purple or red coloration, 
swelling or pain? 
 
Very thanks Miss ______________ with this call we would like to end your participation 
in the study, we thank you very much for your commitment, we hope you continue very 
well, see you soon. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
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Appendix 10: standardized surgical techniques and intra-operative imaging 
manual 
Technical conditions for intraoperative imaging:  
1. 
The taking of photos and videos will be performed by the sub-investigator or 
delegated to a member of the surgical team in case the sub-investigator is not available. 
2. 
The photo taker will use all necessary biosafety items to enter the surgical field.  
3. 
The taking of photos and videos may be done by means of a mobile device camera 
or a standard or professional camera.  
4. 
The taking of photos and videos will be done in a medium, short or detailed 
photographic plane according to the photographic moment to be captured.  
5. 
The photos of the resected macroscopic piece (uterus, uterine segment or placenta) 
will be taken on a clean background to improve its visualization.  
6. 
The format of captured images should be JPEG and the video format should be 
MP4.  
7. 
The maximum duration of each video will be 30 seconds. 
Description of the surgical technique:  
Asepsis and antisepsis of skin and vagina 2. 
Skin incision: Vertical or horizontal. 
3. 
Fascia incision: Vertical or horizontal 
4. 
Dissection by planes up to the abdominal cavity  
5. 
Identification of findings: (Take photo presence or absence of PAD). 
6. 
Intraoperative staging: 
a. 
Opening of the right parametrium: (Take photo) 
b. 
Left parametrial opening: (Take photo) 
c. 
Retrovesical dissection: (Take photo) 
d. 
Vesicouterine bypass: description of the findings (fibrosis?) 
7. 
Hysterotomy:  
8. 
Management of placenta previa or placenta previa: Ward's maneuver.  
9. 
Fetal extraction: time, presentation, weight, length, APGAR, amniotic fluid 
characteristics. 
a. 
Clamping, cutting and ligation of the umbilical cord. 
b. 
Delivery: Does spontaneous delivery occur? Yes/No 
10. 
Hysterotomy management: Hysterorrhaphy or hemostasis with forceps? 
11. 
Vesicouterine dissection is completed 
12. 
Partial myometrial resection vs. total or subtotal hysterectomy. 
a. 
Partial myometrial resection: 
i. 
Hemostatic sutures obliterating colpouterine pedicles. 
ii. 
Resection of abnormal myometrium (segmentectomy) with 
attached placenta (Take photo). 
iii. 
Complete placental delivery 
iv. 
Control of bleeding placental insertion bed (if applicable). 
v. Uterine reconstruction with two layers of suture, the first with "U" 
stitches and the second with invaginating uninterrupted suture (Take 
photo). 
vi. 
Revision of hemostasis of the anterior face of the uterus and 

  
 
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posterior face of the bladder. 
vii. 
Describe if uterine compressive sutures are required. 
 
b. 
Hysterectomy 
i. 
Sequential clamping, cutting and ligation of round ligaments, 
ovarian uterus, uterine arteries, uterosacral ligaments and vaginal vault. 
ii. 
Vaginal vault is fixed with uterosacral ligaments. 
iii. 
Review of hemostasis bases of parametrium and posterior aspect of 
bladder. 
iv. 
Take a photo of the extracted surgical specimen.  
13. 
Counting of complete compresses 
14. 
Closure of the abdominal wall in planes 
a. 
Fascia with ___ 
b. 
Skin with ____ 
 
 
Photos list 
 
Partial myometrial resection 
Hysterectomy 
1.Step 5: Identifyng of surgical findigns 
1.Step 5: Identifyng of surgical findigns 
2.Step 6: A. Right parametrial opening 
2.Step 6: A. Right parametrial opening 
3.Step 6: B. Left parametrial opening 
3.Step 6: B. Left parametrial opening 
4.Step 6: C. Retrovesical dissection 
(Pelosi) 
4.Step 6: C. Retrovesical dissection 
(Pelosi) 
5.Step 12: A.II. Resection of abnormal 
myometrium 
(segmentectomy) 
with 
attached placenta 
5.Step 
12: 
B.V. 
extracted 
surgical 
specimen 
5.Step 12: A.V. Uterine reconstruction 
with two layers of suture 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
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Appendix 11: Standard surgical note 
 
Surgical informed consent 
 
1. Asepsis and antisepsis of skin and vagina. 
2. Skin incision: 
 
3. 
Incision in fascia: 
 
4. 
Dissection by planes up to the abdominal cavity 
5. 
Identification of findings:  
6. 
Intraoperative staging: 
a. 
Right parametrial opening:   
b. 
Left parametrial opening:  
c. 
Retrovesical dissection - Pelosi maneuver:  
d. 
Vesicouterine bypass:  
7. 
Hysterotomy:  
8. 
Management of placenta previa:  
9. 
Fetal extraction: time, presentation, weight, length, APGAR and amniotic fluid 
characteristics. 
a. 
Clamping, cutting and ligation of the umbilical cord. 
b. 
Delivery: spontaneous delivery occurs:  
10. 
Hysterotomy management: hysterorrhaphy or hemostasis with forceps: 11. 
11. 
Vesicouterine dissection is completed 
12. Myometrial partial resection vs. total or subtotal hysterectomy 
a. 
Partial myometrial resection: 
i. 
hemostatic sutures obliterating colpouterine pedicles 
ii. 
Resection of abnormal myometrium (segmentectomy) with 
attached placenta.  
iii. 
Complete placental delivery 
iv. 
Control of bleeding placental insertion bed (if applicable). 
v. Uterine reconstruction with two layers of suture, the first with "U" 
stitches and the second with invaginating uninterrupted suture.  
vi. 
Revision of hemostasis of the anterior face of the uterus and 
posterior face of the bladder. 
vii. 
Describe if uterine compressive sutures are required. 
 
b. 
Hysterectomy 
i. 
Sequential clamping, cutting and ligation of round ligaments, 
ovarian uterus, uterine arteries, uterosacral ligaments and vaginal vault. 
ii. 
Vaginal vault is fixed with uterosacral ligaments. 
iii. 
Review of hemostasis bases of parametrium and posterior aspect of 
bladder. 
iv. 
Take a photo of the extracted surgical specimen.  
 
13. 
Counting of complete compresses 
14. 
Closure of the abdominal wall in planes 
a. 
Fascia with PDS 
b. 
Skin with prolene 
 

  
 
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Complications: 
1. Cystotomy:  
2. 
Ureteral injury:  
3. 
Other: 
 
 
The following variables of interest for the study are verified: 
 
Screening failure: YES / NO   
Gestational age at birth: SS 
 
Time of start of procedure (Skin incision): 00h:00min (24h format) 
Time of end of procedure (Skin closure): 00h:00min (24h format) 
Type of anesthesia used in the procedure: ............................................. 
Type of skin incision: .............................................. 
Type of uterine incision: .............................................. 
Use of vascular interventions: YES / NO. 
Use of Cell saver: YES / NO   
Status of the newborn: Alive / Dead 
Weight:  grams. 
 
Estimated bleeding by count and weight of soaked pads: 0000cc. 
Estimated bleeding by calibrated vaginal collection bag: 00cc 
Estimated bleeding by suction devices: 0000cc 
Total intraoperative bleeding: 0000cc 
 
FIGO classification for PAS: Grade.........  
Topographic classification of PAS: ........................... 
Classification according to Palacios Jaraquemada: Type................ 
 
Blood component transfusion: YES / NO   
Administration of lyophilized fibrinogen: YES / NO   
Uterine tamponade with hydrostatic balloons: YES / NO   
Bladder injury: YES / NO   
Ureteral injury: YES / NO   
Intestinal injury: YES / NO   
 
Intraoperative bleeding:  
1. Quantified bleeding when weighing the compresses:  
2. Quantified bleeding on suction devices:  
Quantified bleeding in pelvic collecting bag:  
 
Use of cell saver: 
 
Transfusion during surgery: 
 
Recording of operative time. 
Time of onset of anesthesia:  

  
 
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2. 
Time of start of surgery (Skin incision):  
3. 
Time of birth:  
4. 
Time of completion of surgery (Skin Closure):  
 
Type of Anesthesia used in the surgical procedure:  
 
Vascular Interventions:  
 
Clinical Diagnosis: 
1.         Presence of PAS:  
2. 
FIGO Classification:  
3. 
Topographic classification:  
4. 
Palacios Jaraquemada Classification: