Aortic Compression Trial to Reduce Blood Loss at Cesarean Section (ACT)

Aortic Compression Trial - a Randomized Controlled Trial to Reduce Blood Loss at Cesarean Section (ACT)

The goal of this clinical trial is to test if manual external aortic compression can prevent heavy blood loss in cesarean section. The main question[s] it aims to answer are:

1. Is external aortic compression effective?
2. Is external aortic compression safe?

Participants will receive preventive manual external aortic compression or no external aortic compression (standard care) immediately after the baby is out at cesarean section. Blood loss will be measured, as well as kidney function, hemoglobin, and hematocrit before and after the operation. Experienced discomfort will be assessed the day after surgery and breastfeeding and signs of depression will be assessed using questionnaires after 2 months.

Researchers will compare women with and without manual external aortic compression to see if there are differences in these outcomes.

Study Overview

• Status: Enrolling by invitation
• Conditions: Anemia; Cesarean Section Complications; Post Partum Hemorrhage
• Intervention / Treatment: Procedure: External aortic compression

Detailed Description

The Aortic Compression Trial (ACT) - A randomized controlled trial to reduce blood loss in cesarean delivery

PURPOSE AND AIMS The purpose is to reduce the prevalence of severe postpartum hemorrhage (PPH), causing maternal mortality and morbidity worldwide. The aim is to investigate if routine manual external aortic compression (EAC) in cesarean delivery (CD) is an effective and safe measure to prevent severe PPH, in a multicenter randomized controlled superiority trial.

SURVEY OF THE FIELD Severe PPH is defined as blood loss >1000 ml at childbirth. Severe PPH is associated with 25% of maternal mortality worldwide and the leading cause of severe morbidity, such as cardiac, respiratory or renal failure and hysterectomy, notably in low-income countries. PPH also entails blood transfusion, anemia, prolonged postpartum recovery, and depression. The global prevalence of severe PPH is 6%. In Sweden, severe PPH occurs in 7% in vaginal birth, 12% in elective CD, and 17% in emergency CD with large variation between hospitals. Routine intravenous oxytocin is recommended to prevent PPH in CD. Several mechanical methods may treat excessive bleeding, but none has been assessed for prevention of PPH. One method for temporizing blood loss is manual external aortic compression (EAC), usually applied until appropriate care is available, for example during transport. The aorta is compressed by placing a fist onto the aorta through the abdominal wall which cuts off the blood supply to the uterus and hence reduces uterine bleeding. A Cochrane review in 2020 (by Kellie et al) stated that high-quality randomized trials into mechanical and surgical methods for the treatment of PPH are urgently needed. Swedish SBU stated in 2022 that prevention of complications in CD is a top prioritized research area. WHO stated in the Global Summit on PPH 2023 that research on PPH should be prioritized to reach global goals on maternal health. The effect or safety of preventive manual EAC has never been evaluated in a clinical trial.

STUDY DESIGN A multicenter randomized controlled superiority trial (RCT) using 1:1 randomization and intention-to-treat analysis. Randomization will be stratified by site using randomized permuted blocks. Core outcomes for prevention of PPH will be reported (8).

Main research questions

Does routine EAC in patients with term/near term pregnancies undergoing elective CD:

1. Reduce the prevalence of severe PPH?
2. Reduce severe morbidity and/or mortality in women?

PICO Population: Patients undergoing elective CD. Intervention: Manual external aortic compression immediately after delivery of the baby until the bleeding from the uterine incision is controlled, usually with the first suture row of uterine incision closure. Cord clamping will be timed and performed regardless of EAC.

Control: No manual external aortic compression, unless deemed vital (standard care).

Outcome: Primary: calculated blood loss >1000 ml or blood transfusion within 2 days.

Other exploratory and safety questions are if EAC affects average blood loss; postpartum hemoglobin or hematocrit levels; time in surgery; pain, breathing, nausea or overall patient experience during surgery; conversion to general anesthesia; use of extra medication during surgery for pain, uterine tone, blood pressure, or blood loss; maternal kidney function; duration of hospital stay postpartum; neonatal outcomes; maternal well-being after childbirth; healing of the uterine scar; or healthcare costs.

Variables and measures Primary Endpoint The primary endpoint is severe postpartum hemorrhage, defined as a calculated estimated blood loss greater than 1000 ml or a red-cell transfusion within 48 hours after delivery. The calculated estimated blood loss = the estimated blood volume × (preoperative hematocrit - postoperative hematocrit) ÷ preoperative hematocrit. The maternal blood volume in milliliters is calculated as the admission body weight in kilograms × 85.

Secondary Endpoints

In clinical routine, blood loss is measured gravimetrically by collecting the blood in canisters and weighing gauzes and drapes, including vaginal bleeding, up to 2 hours after CD. This outcome is also source for the diagnostic codes O67.8 and O72.1. In accordance with the recommended core outcome set (9), five important measures of severe PPH are designated as secondary endpoints:

1. Gravimetrically estimated blood loss >1000 ml within 2 hours of childbirth or red-cell transfusion within 48 hours after childbirth (binary)
2. Total blood loss (in g) up to 2 hours after childbirth (continuous)
3. Red-cell transfusion within 48 hours after childbirth (binary)
4. Composite outcome of transfer to higher level care (intensive care or similar), prolonged stay in post anesthesia care >4 hours, or prolonged postnatal hospital care >4 days (binary)
5. Composite outcome of hypovolemic shock, hysterectomy, uterine tamponade, uterine artery ligation or embolization treatment or other re-operation for internal or vaginal hemorrhage, surgical trauma to bladder, ureters or intestines, thromboembolism, organ failure, cardiac arrest, or maternal death within 42 days (binary).

Exploratory endpoints

Blood loss:

1. Venous B-hemoglobin 1-3 days after childbirth (continuous)
2. Hematocrit 1-3 days after childbirth (continuous)
3. Anemia diagnosed within 7 days postpartum (B-hemoglobin <100 g/l) (binary)

Morbidity (including use of resources):

1. Analgetic treatment in addition to regional anesthesia during surgery or conversion to general anesthesia (binary)
2. Pharmacological treatment for low blood pressure during surgery (phenylephrine, ephedrine, norepinephrine, intravenous crystalloid fluids) (binary)
3. Use of additional uterotonic drugs (>5 IU oxytocin) (binary)
4. Use of hemostatic drugs (e.g., tranexamic acid) (binary)
5. Use of intravenous iron replacement therapy (ferric carboxymaltose) (binary)
6. S-creatinine 1-3 days after childbirth (continuous)
7. Glomerular filtration rate 1-3 days after childbirth (continuous)
8. Start-to-finish surgery duration (min) (continuous)
9. Days in postnatal care (mother) from operation finish time to discharge (continuous)
10. B-hemoglobin at postnatal visit 8-12 weeks after delivery (continuous)

Patient well-being, satisfaction, and acceptability:

1. Perioperative pain (numeric rating scale 0-10)
2. Perioperative breathing discomfort (numeric rating scale 0-10)
3. Perioperative nausea (numeric rating scale 0-10)
4. Perioperative overall experience (numeric rating scale 0-10)
5. Edinburgh Postnatal Depression Scale at 6-8 weeks postpartum
6. Self-rated health 6-12 weeks postpartum (Likert scale 0-5, retrieved from the Swedish Pregnancy Register [SPR])

Neonatal outcomes:

1. Apgar score at 5 minutes <7 (binary)
2. Apgar score at 10 minutes <6 (binary)
3. Neonatal acidosis (cord pH <7.0) (binary)
4. Admission to neonatal care (binary)
5. Neonatal hyperbilirubinemia (binary)
6. Neonatal anemia (binary)
7. Time to cord clamping (min, continuous)
8. Severe neonatal adverse event composite outcome (hypothermic treatment, hypoxic ischemic encephalopathy grade 2¬-3, or neonatal death within 28 days) (binary)
9. Breastfeeding Self-Efficacy Scale short form at 6-8 weeks postpartum
10. Self-reported breastfeeding 6-12 weeks postpartum (retrieved from SPR)

Long-term health:

1. Uterine scar healing measured by sonographic evaluation of the hysterotomy scar at 6-12 months after delivery (mean anterior wall thickness, prevalence of a niche)
2. Uterine rupture in the subsequent childbirth, scar dehiscence, or isthmocele surgery (5-year register-based follow-up)

Cost-effectiveness and healthcare costs: This will be detailed in a separate analysis plan and calculated including the first 42 days postpartum based on an estimated cost for the utilization of medical resources preliminary including (but not limited to):

• Duration of surgery
• Blood transfusion and transfusion of other blood products
• Intensive care
• Maternal and neonatal length of hospital stay
• Number of maternal visits postpartum

Material: Patient selection - population, sample The trial will include patients undergoing elective CD to facilitate timely informed consent. Around 10 000 elective CD are performed annually in Sweden. Patients will be recruited and screened at scheduling or admission for CD. Results will likely be transferrable to emergency CD with higher risk of PPH in which obtaining informed consent is more challenging. Using EAC as preventive method makes safety a high priority (severe adverse effects should be avoided in health individuals). Patients with planned cesarean hysterectomy or preoperative anemia will be excluded since their risk of PPH or blood transfusion postpartum may not be related to blood loss at CD.

Inclusion criteria: Patients with elective CD, live fetus (fetuses if multiple pregnancy), gestational week 34+0 or more.

Exclusion criteria: Preoperative B-hemoglobin <100 g/l, planned cesarean hysterectomy, other condition as deemed by attending surgeon.

Treatment will be allocated in the operating theatre using opaque sealed envelopes professionally prepared by KTA. There is no masking due to the nature of the intervention. Analyses will be blinded for allocated treatment.

Estimated sample size and power Around 12.4% of elective CD have PPH >1000 ml. To demonstrate a clinically relevant relative risk reduction of 30% at 80% power, n=1069 women in each treatment arm is needed, assuming significance level α=0.05, two-sided test. The sample size will be inflated by 5% to account for drop-out and heterogeneity between centers, resulting in total sample size n=2246 women. This sample size is also sufficient to detect relatively rare outcomes, such as intensive care or hysterectomy. Sample size calculations were performed by using the POWER procedure in SAS/STAT Software, version 9.4 of the SAS System for Windows (SAS Institute Inc., Cary, NC).

Statistical methods The primary efficacy analysis will be based on the intention-to-treat (ITT) population using a generalized linear mixed-effects model with log-link, Poisson distribution, treatment as fixed effect and site as random effect to estimate the relative risk of event while accounting for center effects. Using this model, the 80% power for the primary endpoint will be retained provided that recruitment is terminated with complete blocks, i.e., with balanced treatment allocation at all sites (12). Similar methods will be employed for secondary and exploratory endpoints using appropriate models and distributions depending on the type and distribution of the outcome, i.e., Poisson model to estimate the relative risk of binary events (e.g., maternal composite outcome), log-normal distribution for continuous and positively skewed outcomes (e.g., duration of surgery), negative binomial distribution for counts (e.g., days in hospital), and normal distribution for other numeric outcomes. Patient-reported outcomes and questionnaire scales will be treated as numeric in this regard. All estimates will be provided with 95% confidence intervals. If the primary endpoint is significant, the secondary endpoint maternal composite outcome will be confirmatory tested at the 5% significance level. All safety outcomes will be presented for both the ITT population and the safety population (all randomized women according to actual treatment). The statistical analysis plan will be established in detail and documented before data lock. Responsible statistician is Henrik Imberg, PhD, at Statistiska Konsultgruppen Sweden AB.

FEASIBILITY The trial has received a planning grant (VR 2021-06579), ethical approval Sept 20, 2022 from the Swedish Ethical Review Authority (2022-04327-01) with amendment approved Dec 20, 2022 (2022-06377-02), and formal support from www.snaks.se. The trial has started at one site (Danderyd) Dec 1, 2022, and had recruited 317 patients by Jan 19, 2025 (30% of elective CD) and proven acceptable both to patients and physicians. Nine hospitals in five regions have agreed to participate in the trial: Danderyd, Karolinska Huddinge and Solna, Södersjukhuset, Södertälje, Norrköping, Falun, Uppsala, and Göteborg. These sites perform approximately 3500 elective CD per year (www.graviditetsregistret.se).

We have assessed safety outcomes after 156 randomized patients. EAC was applied during mean 8.7 minutes (median 9, range 1-22). There were no clinically or statistically significant differences between the groups regarding safety outcomes (P-Creatinine postoperative (µmol/l), P-GFR postoperative (ml/min), overall maternal experience, umbilical vein pH, umbilical vein pO2, Apgar 5 min <7, or admission to neonatal care.

• Study Type: Interventional
• Enrollment (Estimated): 2246
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • Danderyd Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Planned cesarean delivery
• Live fetus/fetuses if multiple pregnancy
• Gestational week 34+0 or more

Exclusion Criteria:

• Preoperative B-Hemoglobin <100 g/l
• Planned hysterectomy in the same procedure as the planned cesarean delivery
• Other condition as deemed by attending surgeon.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No external aortic compression; No routine aortic compression. If deemed vital to the mother, aortic compression should be exerted. Aortic compression may be exerted if bleeding exceeds 1000 ml.
Experimental: Routine external aortic compression; The assistant surgeon or nurse places heel of the hand or fist over the abdominal aorta immediately after the baby is born while the surgeon helps the baby out, the placenta is expulsed or fetched, and the surgeon gains control over bleeding. The compression should be held until controlled bleedning, for example until the first layer of the uterine incision is sutured. Maximum time of aortic compression is 20 minutes, then a 5 minute break is required, after which compression may be reapplied.	Procedure: External aortic compression; External aortic compression by assistant in cesarean section.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculated peripartum hemorrhage	Calculated estimated blood loss greater than 1000 ml or a red-cell transfusion within 48 hours after delivery. The calculated estimated blood loss = the estimated blood volume × (preoperative hematocrit - postoperative hematocrit) ÷ preoperative hematocrit. The estimated blood volume in milliliters is calculated as the admission body weight in kilograms × 85.	0-2 days postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gravimetrically estimated peripartum hemorrhage (g) or blood transfusion	Gravimetrically estimated blood loss >1000 ml within 2 hours of childbirth or red-cell transfusion within 48 hours after childbirth (binary)	0-2 hours postpartum
Total blood loss	Total blood loss (in g) up to 2 hours after childbirth (continuous).	0-1 days postpartum
Transfusion	Red-cell transfusion within 48 hours after childbirth (binary).	0-2 days postpartum
Maternal higher-level care	Composite outcome of transfer to higher level care (intensive care or similar), prolonged stay in post anesthesia care >4 hours, or prolonged postnatal hospital care >4 days (binary).	0-7 days postpartum
Severe maternal morbidity	Composite outcome of hypovolemic shock, hysterectomy, uterine tamponade, uterine artery ligation or embolization treatment or other re-operation for internal or vaginal hemorrhage, surgical trauma to bladder, ureters or intestines, thromboembolism, organ failure, cardiac arrest, or maternal death within 42 days (binary).	0-42 days postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood loss, exploratory outcome B-Hb	Venous B-hemoglobin 1-3 days after childbirth (continuous)	0-7 days postpartum
Blood loss, exploratory outcome B-EVF (hematocrit)	Hematocrit 1-3 days after childbirth (continuous) 3. Anemia diagnosed within 7 days postpartum (B-hemoglobin <100 g/l) (binary)	0-7 days postpartum
Blood loss, exploratory outcome Anemia	Anemia diagnosed within 7 days postpartum, defined as B-hemoglobin <100 g/l (binary)	0-7 days postpartum
Morbidity (including use of resources) - Extra analgetic treatment	Analgetic treatment in addition to regional anesthesia during surgery or conversion to general anesthesia (binary)	0-1 hour postpartum
Morbidity (including use of resources) - Extra blood pressure treatment	Pharmacological treatment for low blood pressure during surgery (phenylephrine, ephedrine, norepinephrine, intravenous crystalloid fluids) (binary)	0-1 hour postpartum
Morbidity (including use of resources) - Extra uterotonics	Use of additional uterotonic drugs (>5 IU oxytocin) (binary)	0-4 hours postpartum
Morbidity (including use of resources) - Hemostatic drugs	Use of hemostatic drugs (e.g., tranexamic acid) (binary)	0-4 hours postpartum
Morbidity (including use of resources) - IV iron treatment	Use of intravenous iron replacement therapy (ferric carboxymaltose) (binary) 6. S-creatinine 1-3 days after childbirth (continuous) 7. Glomerular filtration rate 1-3 days after childbirth (continuous) 8. Start-to-finish surgery duration (min) (continuous) 9. Days in postnatal care (mother) from operation finish time to discharge (continuous) 10. B-hemoglobin at postnatal visit 8-12 weeks after delivery (continuous)	0-2 weeks postpartum
Morbidity (including use of resources) - Kidney function postpartum	Affected S-creatinine 1-3 days after childbirth (dichotomous) or Glomerular filtration rate 1-3 days after childbirth (dichotomous)	0-3 days postpartum
Morbidity (including use of resources) - Surgery duration	Start-to-finish surgery duration (min) (continuous)	0-1 day postpartum
Morbidity (including use of resources) - Hospital stay duration	Days in postnatal care (mother) from operation finish time to discharge (continuous)	0-4 weeks postpartum
Morbidity (including use of resources) - B-Hb postnatal visit	B-hemoglobin at postnatal visit 8-12 weeks after delivery (continuous)	8-12 weeks postpartum
Patient well-being, satisfaction, and acceptability - Perioperative pain	Perioperative pain (numeric rating scale 0-10) Pain, nausea, breathing discomfort, overall experience rated with numeric rating scale 0-10 where 0 is no pain/nausea/breathing discomfort and 10 is maximum pain/nausea/breathing discomfort. Experience is assessed as 0=worst and 10=best possible.	1-3 days postpartum
Patient well-being, satisfaction, and acceptability - Perioperative breathing	Perioperative breathing discomfort (numeric rating scale 0-10) Pain, nausea, breathing discomfort, overall experience rated with numeric rating scale 0-10 where 0 is no pain/nausea/breathing discomfort and 10 is maximum pain/nausea/breathing discomfort. Experience is assessed as 0=worst and 10=best possible.	1-3 days postpartum
Patient well-being, satisfaction, and acceptability - Perioperative nausea	Perioperative nausea (numeric rating scale 0-10) Pain, nausea, breathing discomfort, overall experience rated with numeric rating scale 0-10 where 0 is no pain/nausea/breathing discomfort and 10 is maximum pain/nausea/breathing discomfort. Experience is assessed as 0=worst and 10=best possible.	1-3 days postpartum
Patient well-being, satisfaction, and acceptability - Perioperative overall exp	Perioperative overall experience (numeric rating scale 0-10) Pain, nausea, breathing discomfort, overall experience rated with numeric rating scale 0-10 where 0 is no pain/nausea/breathing discomfort and 10 is maximum pain/nausea/breathing discomfort. Experience is assessed as 0=worst and 10=best possible.	1-3 days postpartum
Patient well-being, satisfaction, and acceptability - EPDS	Edinburgh Postnatal Depression Scale at 6-8 weeks postpartum	6-8 weeks postpartum
Patient well-being, satisfaction, and acceptability	Self-rated health 6-12 weeks postpartum (Likert scale 0-5, retrieved from the Swedish Pregnancy Register [SPR])	6-12 weeks postpartum
Neonatal outcomes - 5 min Apgar <7	Apgar score at 5 minutes <7 (binary)	0-1 day postpartum
Neonatal outcomes - 10 min Apgar <6	Apgar score at 10 minutes <6 (binary)	0-1 day postpartum
Neonatal outcomes - Neonatal acidosis	Neonatal acidosis (cord pH <7.0) (binary) at birth	0-1 day postpartum
Neonatal outcomes - NICU admission	Admission to neonatal care (binary) within first 7 days	0-7 days
Neonatal outcomes - Hyperbilirubinemia	Neonatal hyperbilirubinemia (binary) within first 7 days	0-7 days
Neonatal outcomes - Neonatal anemia	Neonatal anemia (binary) within first 7 days	0-7 days
Neonatal outcomes - Cord clamping	Time to cord clamping (min, continuous)	0-1 days postpartum
Neonatal outcomes - Severe adverse composite outcome	Any of hypothermic treatment, hypoxic ischemic encephalopathy grade 2-3, or neonatal death within 28 days) (binary)	0-28 days postpartum
Neonatal outcomes - Breastfeeding self-efficacy	Breastfeeding Self-Efficacy Scale short form at 6-8 weeks postpartum	6-8 weeks postpartum
Neonatal outcomes - Breastfeeding self-reported	Self-reported breastfeeding 6-12 weeks postpartum (retrieved from SPR)	6-12 weeks postpartum
Long-term maternal health - uterine scar healing	Sonographic evaluation of the uterine scar at approx. 12 months after childbirth (anterior wall thickness <3 mm or visible niche)	6-18 months
Long-term maternal health - subsequent birth outcomes	Uterine rupture or dehiscence in the subsequent childbirth (register-based follow-up)	5 years
Long-term maternal health - isthmocele	Isthmocele diagnosis or surgery (5-year register-based follow-up)	5 years
Cost-effectiveness and healthcare costs	This will be detailed in a separate analysis plan and calculated including the first 42 days postpartum based on an estimated cost for the utilization of medical resources preliminary including (but not limited to): Duration of surgery; Blood transfusion and transfusion of other blood products; Intensive care; Maternal and neonatal length of hospital stay; Number of maternal visits postpartum	0-42 days postpartum

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: The Swedish Research Council
• Investigators: Principal Investigator: Sophia Brismar Wendel, MD, PhD, Danderyd Hospital Karolinska Institutet, Sweden

Publications and helpful links

General Publications

• Kellie FJ, Wandabwa JN, Mousa HA, Weeks AD. Mechanical and surgical interventions for treating primary postpartum haemorrhage. Cochrane Database Syst Rev. 2020 Jul 1;7(7):CD013663. doi: 10.1002/14651858.CD013663.

Helpful Links

• Swedish network for national clinical studies in Obstetrics and Gynecology, information about ACT in Swedish

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: May 30, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; Cesarean section; Post partum hemorrhage; Aortic compression
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Puerperal Disorders; Uterine Hemorrhage; Postpartum Hemorrhage; Hemorrhage
• Other Study ID Numbers: 2021-06579

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data will be shared with other researchers for a joint publication or for systematic review purposes with due citation.
• IPD Sharing Time Frame: From one year after the trial is finalized with no upper limit.
• IPD Sharing Access Criteria: To be defined
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No