ABSTRACT
Objective
Uncertainty surrounds the risk–benefit of low‐molecular‐weight heparin to prevent postpartum venous thromboembolism (VTE). Data from randomised clinical trials (RCT) are critically needed, but recent feasibility studies in North America yielded low participation rates, with <1 enrolment per month per centre. Our aim was to assess the feasibility of a trial of postpartum short‐term enoxaparin in Europe.
Design
Pragmatic, open‐label pilot randomised controlled trial (RCT).
Setting
Swiss tertiary hospital.
Population
Postpartum women, within 48 h of delivery, deemed at intermediate risk of VTE with at least one major risk factor (morbid obesity, thrombophilia, emergency caesarean section, pre‐eclampsia, preterm delivery, intrauterine growth restriction or systemic peripartum infection) and/or at least two minor risk factors.
Methods
Participants were randomised to enoxaparin 40–60 mg once daily for 10 days or no treatment, with a 90‐day follow‐up.
Main Outcome Measures
Participation rate and study acceptance (randomised participants among women in whom informed consent was sought).
Results
Recruitment was open for 25 weeks in 2022. Among 1504 postpartum women, 480 were eligible and 77 were randomised. The recruitment rate was 3.1 per week (13.3 per month) and the study acceptance was 23.8%. At 3 months, there was no VTE event, but one major, one nonmajor obstetrical bleeding and one surgical site complication, all in the enoxaparin group.
Conclusions
This pilot RCT of postpartum thromboprophylaxis set in Switzerland yielded greater participation rate and acceptance than previous attempts in North America. It calls for a large, international, collaborative trial to guide this important clinical decision.
Trial Registration
ClinicalTrial.gov identifier: NCT05878899 and NCT04153760.
Keywords: low‐molecular‐weight heparin, postpartum, pregnancy, venous thrombosis
1. Introduction
Pregnancy‐associated venous thromboembolism (VTE) accounts for about 10% of VTE in women and is responsible for substantial morbidity and mortality [1, 2, 3]. Its incidence is greatest in the postpartum period, with a peak of risk in the first 2 weeks after delivery and >10 000 postpartum VTE cases annually in Europe. This has led to some use of low‐molecular‐weight heparin (LMWH) after delivery to reduce the burden of VTE, albeit with a lack of direct evidence. The thromboprophylaxis guidance is very heterogeneous across the world [4, 5, 6] and this is particularly true for women at intermediate risk of postpartum VTE, with some risk factors but no previous history of VTE or severe thrombophilia.
The clinical importance of understanding the benefit–risk of low‐dose LMWH in the postpartum period has long been identified [7, 8, 9, 10] but no large‐scale randomised clinical trial (RCT) has been attempted or conducted, and evidence from nonrandomised studies is too limited to guide clinical practice [11]. The major barrier is the recruitment of a sample size large enough to bring conclusive evidence, with previous feasibility pilot trials showing a disappointingly low recruitment rate [12, 13].
The goal of the postpartum heparin (PP‐HEP) pilot study is to evaluate in a Swiss tertiary maternity the feasibility of recruitment and conduct of a simple, pragmatic, open‐label randomised controlled trial of short‐term low‐dose LMWH after delivery, among women with risk factors for VTE.
2. Methods
The PP‐HEP pilot study is a prospective, monocentric, open‐label randomised controlled trial of adult women set at the Geneva University Hospitals, Switzerland. We obtained ethics approval (Commission cantonale d'éthique de la recherche, Genève, #2021‐02350, 21/02/2021) and individual written consent from all participants. The study is registered at clinicaltrials.gov (NCT05878899) and was funded by a grant from the Geneva University Hospitals (PRD 4‐2019‐II), which had no influence on the study. The original protocol is accessible upon request to the corresponding author.
2.1. Population
We recruited adult women aged ≥18 years, deemed at intermediate risk of postpartum VTE, who gave birth at the Geneva University Hospitals (4160 births in 2022). Women were eligible if they had ≥1 of the following risk factors: emergency caesarean section (C‐section); prepregnancy body mass index (BMI) ≥35 kg/m2; a known low‐risk thrombophilia (heterozygous factor V Leiden or heterozygous G20210 prothrombin mutation); pre‐eclampsia; preterm delivery (<37 weeks of gestation); peripartum systemic infection; intrauterine growth restriction (birth weight < 5th percentile); and/or ≥2 of the following risk factors: age ≥ 35 years, prepregnancy BMI of 30–34.9 kg/m2, current smoking, elective C‐section, postpartum haemorrhage (≥500 mL after vaginal delivery or ≥1000 mL after C‐section) and antenatal immobility (≥72 h within the month prior to birth). Exclusion criteria were language barrier (not fluent in French or English), psychological issues (postpartum distress, as appreciated by the caregivers), stillbirth, any indication for therapeutic anticoagulation, a high risk of postpartum VTE (personal history of VTE or high‐risk thrombophilia), an increased bleeding risk (known bleeding disorder, active postpartum bleeding, platelets <50 g/L, severe renal [GFR < 30 mL/min] or liver disease, uncontrolled hypertension and an increased bleeding risk as deemed by the physician in charge) and a contraindication to the use of heparin.
Women were recruited and randomised within 48 h of delivery. This timeframe was viewed as the best trade‐off between study feasibility and clinical efficacy to protect against early VTE events. The administration of one dose of prophylactic low‐molecular‐weight heparin prior to study inclusion was permitted.
We had initially planned to recruit women both in the antenatal and postpartum periods but found antenatal screening procedures to be inefficient. Thus, only women in their postpartum period were screened and approached for study inclusion.
2.2. Study Intervention
In the intervention group, women received enoxaparin 20 mg (postpartum body weight < 50 kg), 40 mg (50–100 kg) or 60 mg (>100 kg) once daily, subcutaneously, for 10 days after delivery or the duration of the postpartum hospital stay if it extended beyond 10 days. In the control group, women did not receive any pharmacological thromboprophylaxis after study inclusion. We chose 10 days to efficiently reduce the known peak of postpartum VTE incidence of the first 2–3 weeks [14, 15], to match the current RCOG guidelines and to maintain an acceptable duration of injections for women.
The current standard practice at the time in our hospital was to provide in‐hospital low‐dose LMWH mainly in women after C‐section. There was no guidance for the use of mechanical thromboprophylaxis.
2.3. Study Procedures
Delivering women from the last 48 h were inspected using the hospital's electronic medical charts to assess eligibility for the study. Then, we approached eligible women and obtained written informed consent. Recruitment was mainly done by a study midwife, employed at 50% during the study period. Participating women were randomised 1:1 between the intervention and control groups, with permuting blocks of two to six stratified by vaginal deliveries and C‐sections, in an open‐label fashion. Those randomised to enoxaparin were provided study drugs and were trained for subcutaneous injections at the time of discharge, for a total duration of 10 days. We instructed women orally and in writing to seek medical consultation and/or alert study staff in case of symptoms suggestive of VTE events, bleeding events or problems with the study drug.
The study follow‐up was 90 days after delivery, with three telephone visits (Day 10, Day 42 and Day 90). At each visit, we assessed symptoms suggestive of study outcomes and serious adverse outcomes. For women in the intervention group, we evaluated study drug compliance orally and asked them to complete a treatment satisfaction questionnaire online on Day 10.
2.4. Study Outcomes
In this feasibility study, the primary outcomes were the recruitment rate, measured by the number of women randomised per week or per month, and the study acceptance, measured by the proportion of randomised participants among eligible women in whom informed consent was sought. Secondary feasibility outcomes included the reasons for study nonparticipation (categorised into fear of injection, thrombosis or bleeding; an important postpartum emotional charge [burden]; and the study treatment deemed unnecessary), loss to follow‐up and study drug compliance.
As clinical outcomes, we evaluated VTE, septic pelvic thrombophlebitis, all‐cause mortality, nonobstetrical and obstetrical bleeding, heparin‐induced thrombocytopenia (without laboratory screening) and C‐section site complication. Venous thromboembolism was defined as an objective diagnosis of symptomatic or unsuspected proximal lower extremity deep vein thrombosis (DVT), symptomatic distal lower extremity DVT, pulmonary embolism or symptomatic proximal upper extremity. Objective imaging included lower limb venous compression ultrasound, CT pulmonary angiogram and/or ventilation/perfusion lung scintigraphy. No screening for VTE was performed. Septic pelvic thrombophlebitis was defined by fever and an objectively diagnosed ovarian or pelvic thrombus. Using the 2019 ISTH proposal for obstetrical and nonobstetrical bleeding [16], we defined obstetrical major bleeding as overt obstetrical bleeding leading to death, associated with a fall of haemoglobin level of ≥20 g/L and/or leading to the transfusion of ≥2 units of blood. Obstetrical clinically relevant nonmajor bleeding (CRNMB) was defined as obstetrical bleeding leading to hospitalisation or prolongation of hospitalisation, modification of antithrombotic therapy and/or requiring medical intervention by a healthcare professional. Nonobstetrical major bleeding was defined as an acute clinically overt nonobstetrical bleeding leading to death, occurring in a critical organ (intracranial, intraspinal, intraocular, retroperitoneal, pericardial, intra‐articular and intramuscular with compartment syndrome), associated with a fall of haemoglobin level of ≥20 g/L and/or leading to the transfusion of ≥2 units of blood. Nonobstetrical CRNMB was defined as nonobstetrical bleeding leading to hospitalisation or increased level of care, prompting a face‐to‐face evaluation and/or requiring medical intervention by a healthcare professional. Center for Disease Control definitions were used for surgical site complications among participants with C‐sections [17], such as superficial incisional surgical site infection, deep incisional surgical site infection, open/space surgical site infection, cellulitis, seroma, haematoma and wound separation, within 30 days of C‐section.
The drug satisfaction questionnaire was the Treatment Satisfaction Questionnaire for Medication (TSQM) version II (Table S1) [18].
2.5. Statistical Analysis
Characteristics of the participants were described as proportions or means, where appropriate. Outcomes were analysed according to the intention‐to‐treat approach, using proportions at 90 days with comparisons across randomised groups with Fisher exact test. We did not plan to test a formal threshold of recruitment rate to assess feasibility but hypothesised a target of five participants per week. A subgroup analysis of delivery method (C‐section vs. vaginal delivery) was not done due to the low number of events.
The study was funded to be conducted for about 6 months, similar to previous pilot studies [12, 13].
No interim analysis was done and no stopping rule was planned. There was no imputation for missing data. All analyses were done with Stata 16.0 (StataCorp LLC, TX, USA).
3. Results
The study was open from May until November 2022, for 25 weeks. We screened charts of 1504 postpartum women, of whom 480 (31.9%) were possibly eligible for study inclusion (flow chart, Figure 1). We proposed the study to 323 women (21.5%; 67.3% of eligible women), of whom 77 (5.1%; 23.8% of approached women) were included and randomised. Among women who refused to participate, the three most common reasons were a fear of subcutaneous injection (53.7%), an overwhelming postpartum emotional charge/burden (19.9%) and the belief that postpartum thromboprophylaxis was unnecessary (17.9%). Thirty‐nine per cent (30/77) of women were randomised on the day of delivery, 51.9% (40/77) the next day after delivery and 9.1% (7/77) close to 48 h after delivery.
FIGURE 1.
Flow chart of the study.
The follow‐up was complete (CONSORT diagram, Figure 2). All participants received the allocated treatment during the first 24 h of the study, except one participant randomised to the no‐treatment group who still requested three injections of enoxaparin 40 mg prior to hospital discharge.
FIGURE 2.
CONSORT diagram.
As primary outcomes, the weekly/monthly enrolment in the study was 3.1/13.3 participants. The study acceptance was 23.8% (95% CI 19.2–28.9).
At baseline, the mean age and prepregnancy BMI were 34.5 years (SD 4.9) and 27.0 kg/m2 (SD 7.4, Table 1). None of the participants had a prior superficial vein thrombosis or cardiovascular disease. Antepartum aspirin or prophylactic LMWH had been administered to 9 women (11.7%), and 31 (40.3%) had received one dose of postpartum LMWH through standard care prior to study inclusion. Delivery had occurred, on average, at 39.1 weeks (SD 1.7). We collected data from routine laboratory tests, however, with missing data: mean haemoglobin of 115 g/L (SD 17.1, n = 55), mean platelets of 215 g/L (SD 63, n = 54) and mean fibrinogen of 5.4 g/L (SD 1.6, n = 24). Most participants had at least one major postpartum inclusion criteria (n = 58, 75.3%), of which an emergency C‐section was the most common.
TABLE 1.
Baseline characteristics of the participants.
| Enoxaparin (n = 39) | Control (n = 38) | |
|---|---|---|
| Age (years) | 33.9 (4.4) | 35.1 (5.2) |
| Prepregnancy weight (kg) | 72.2 (17.4) | 72.3 (21.2) |
| Prepregnancy body mass index (kg/m2) | 27.5 (7.4) | 26.5 (7.4) |
| Prepregnancy BMI > 30 (kg/m2) | 13 (33.3%) | 10 (26.3%) |
| Race/Ethnicity | ||
| Non‐Hispanic white | 31 (79.5%) | 23 (60.5%) |
| Asian | 1 (2.6%) | 4 (10.5%) |
| Hispanic | 5 (12.8%) | 8 (21.1%) |
| African | 1 (2.6%) | 2 (5.3%) |
| Other | 1 (2.6%) | 1 (2.6%) |
| Prepregnancy hypertension | 3 (7.7%) | 1 (2.6%) |
| Prepregnancy diabetes | 1 (2.6%) | 0 |
| First‐degree family history of VTE | 5 (12.8%) | 6 (15.8%) |
| Gravidity | 2.4 (1.6) | 2.6 (2.1) |
| Parity | 1.7 (1.2) | 1.9 (1.1) |
| Gestational hypertension | 3 (7.7%) | 4 (10.5%) |
| Gestational diabetes | 3 (7.7%) | 4 (10.5%) |
| Newborn birth weight (g) | 3203 (442) | 3245 (632) |
| Major inclusion criteria | ||
| Prepregnancy morbid obesity (BMI ≥ 35 kg/m2) | 9 (23.1%) | 5 (13.2%) |
| Low‐risk thrombophilia | 0 | 0 |
| Pre‐eclampsia | 2 (5.1%) | 0 (0%) |
| Preterm delivery | 1 (2.6%) | 4 (10.5%) |
| Peripartum systemic infection | 13 (33.3%) | 10 (26.3%) |
| Intrauterine growth restriction | 2 (5.1%) | 4 (10.5%) |
| Emergency C‐section | 17 (43.6%) | 17 (44.7%) |
| Minor inclusion criteria | ||
| Age ≥ 35 years | 18 (46.2%) | 23 (60.5%) |
| Prepregnancy obesity (BMI 30.0–34.9 kg/m2) | 4 (10.3%) | 5 (13.2%) |
| Current smoking | 5 (12.8%) | 5 (13.2%) |
| Postpartum haemorrhage | 3 (7.7%) | 8 (21.1%) |
| Antenatal immobility | 0 | 0 |
| Elective C‐section | 5 (12.8%) | 5 (13.2%) |
Note: Continuous variables as mean (SD) and categorical variables as n (%).
Abbreviations: BMI, body mass index; VTE, venous thromboembolism.
In the treatment group, four participants (10.3%) received enoxaparin 60 mg and all others enoxaparin 40 mg. The mean duration of treatment from delivery was 8.9 days (SD 1.9), 33 women (84.6%) received ≥8 days of enoxaparin and 24 (61.5%) received the complete 10 days of enoxaparin. Most women who stopped prematurely the study drugs did so because of the burden of injections. In the control group, the mean duration of treatment from delivery, including the possible injection prior to study inclusion, was 0.4 days (SD 0.6).
At 90 days of follow‐up, there was no death, VTE events, septic pelvic thrombophlebitis or heparin‐induced thrombocytopenia (Table 2). Two women in the enoxaparin group suffered from a bleeding complication. One obstetrical major bleeding occurred on Day 46, with a drop of 40 g/L of Hb from vaginal bleeding due to retained placental material, which was treated with hysteroscopy. One obstetrical clinically relevant nonmajor bleeding occurred on Day 44, with vaginal bleeding necessitating a gynaecological assessment, imaging and treatment with tranexamic acid. For surgical site complication, one participant had cellulitis of the C‐section scar treated with antibiotics in the enoxaparin group. All exploratory statistical comparisons were not significant (p = 1.0 for major bleeding; p = 1.0 for nonmajor bleeding; p = 0.49 for major and nonmajor bleeding; and p = 1.0 for surgical site complication).
TABLE 2.
Ninety‐day clinical outcomes.
| Enoxaparin (n = 39) | Control (n = 38) | |
|---|---|---|
| Venous thromboembolism | 0 | 0 |
| Major bleeding | 1 (2.6%) | 0 |
| Obstetrical | 1 (2.6%) | 0 |
| Nonobstetrical | 0 | 0 |
| Clinically relevant nonmajor bleeding | 1 (2.6%) | 0 |
| Obstetrical | 1 (2.6%) | 0 |
| Nonobstetrical | 0 | 0 |
| Surgical site complication a | 1 (4.5%) | 0 |
Among participants with C‐sections.
The TSQM questionnaire was completed by 31/39 (79.5%) participants randomised to enoxaparin. From highest to lowest (100% to 0%), women valued the lack of impact of side effects at an average of 98.1%, the effectiveness of the drug at 70.7%, the global satisfaction at 68.8% and the convenience of the drug at 63.6%. Among the items exploring convenience, 71.0%, 58.1% and 74.1% of women were satisfied, very satisfied or extremely satisfied with the easiness of use, the easiness of planification and the timing of medication. The mean satisfaction score was 68.8% (SD 20.4) and was greater in women who administered ≥8 days of enoxaparin (70.5%) than in women who administered <8 days (52.8%).
We recorded three serious adverse events, with full recovery and deemed not related to the study treatment (n = 2 in the enoxaparin group and n = 1 in the control group). These were an elective change in a medullary neurostimulator on study Day 86, a hysteroscopy for retained placental material on Day 46 and the occurrence of severe pre‐eclampsia on Day 5.
4. Discussion
4.1. Main Findings
In this monocentric feasibility trial, we were able to recruit 5.1% of all deliveries and 23.8% of women who were offered to participate were randomised. Per month, the inclusion rate was 13.3 women. We had no difficulty in the 3‐month follow‐up. Compliance with study drug was satisfactory (≥80% in 84.6% of participants). As expected, the incidence of clinical outcomes was low.
4.2. Interpretation
Our data challenge previous affirmations that recruitment of participants in open‐label RCTs of injectable LMWH in the postpartum period is infeasible. Our recruitment rate and overall patient participation are much greater than recently reported (Table 3) in the North American PROSPER1 and PROSPER2 pilot trials. In PROSPER1, women with low‐risk thrombophilia, immobilisation or two risk factors among postpartum infection, bleeding, BMI ≥ 25 kg/m2, smoking, preeclampsia, IUGR or an emergency C‐section were randomised to dalteparin 5000 IU for 3 weeks versus placebo [13]. The monthly enrolment per centre was 0.7, with only 7% of women accepting to participate. PROSPER2 was similar except for an open‐label design, without subcutaneous placebo injection, and a shorter duration of treatment (10 days instead of 3 weeks), but this led to a very marginal improvement of feasibility (enrolment of 0.9 participant per month, acceptance of 11%) [12]. Two other attempts, >20 years ago, yielded contrasting results, with a very good enrolment and study acceptance in an Australian tertiary centre but low enrolment in UK centres [8, 9].
TABLE 3.
Pilot randomised controlled trials of low‐molecular‐weight heparin for postpartum thromboprophylaxis.
| Design | Region | Inclusion criteria | Achieved sample size | Intervention | Control group | Study acceptance | Enrolment per month per centre | |
|---|---|---|---|---|---|---|---|---|
| Burrows [8] | Monocentric double‐blinded RCT | Australia | Caesarean section | 76 | Dalteparin 2500 IU o.d. (5 days) | Placebo o.d. (5 days) | 53.9% | 15.2 |
| Gates [9] | Multicentre [8] double‐blinded RCT | UK | Caesarean section | 141 | Enoxaparin 40 mg o.d. (maximum 14 days) | Placebo o.d. (maximum 14 days) | n/a | 2.5 |
| Rodger [13] | Multicentre [6] double‐blinded RCT, with a screening ultrasound at 3 weeks | USA, Canada | Low‐risk thrombophilia, immobilisation or combination of risk factors | 25 | Dalteparin 5000 IU o.d. (3 weeks) | Placebo o.d. (3 weeks) | 6.6% | 0.7 |
| Rodger [12] | Multicentre [8] open‐label RCT | USA, Canada | Low‐risk thrombophilia, immobilisation or combination of risk factors | 37 | Dalteparin 5000 IU o.d. (10 days) | No treatment | 10.7% | 0.9 |
| Blondon, 2024 | Monocentric open‐label RCT | Switzerland | Low‐risk thrombophilia, morbid obesity, pre‐eclampsia, preterm delivery, peripartum infection, IUGR, emergency C‐section or combination of risk factors | 77 | Enoxaparin 40–60 mg o.d. (10 days) | No treatment | 23.8% | 13.3 |
Abbreviations: IUGR, intrauterine growth restriction; o.d., once daily; RCT, randomised controlled trial.
Several reasons may explain the observed better recruitment of our study. First, our pilot trial had a pragmatic and simple design, with an open‐label design without placebo, symptomatic outcomes, lack of screening examinations and at‐distance/telephone study visits. While the open‐label introduces a possible detection bias, it maximises the willingness to participate. Second, we used a short‐term duration of treatment (10 days). Third, we assessed feasibility in a unique centre, with motivated study personnel, but acknowledge that the recruitment figures may differ in a multicentric environment. Fourth, we believe that women in Switzerland and Europe, in general, are more likely to participate, given a historically greater prevalence of postpartum thromboprophylaxis than in North America [5, 6] and with longer durations of delivery hospital stays.
Our recruitment rate remained below our hypothesised target of 5 per week, highlighting that the conduct of a clinical in postpartum women remains difficult. However, this target was imagined for the feasibility of a short (2 years) multicentre trial across 20 study centres. With the obtained recruitment of 13.3 participants per month and 5% of inclusions across all deliveries, we believe that a full‐scale trial of postpartum thromboprophylaxis is feasible. Depending on the VTE risk of the target population, sample sizes of such a trial may range from 4000 to 15 000 participants [9, 13]. For instance, to detect a 0.335% absolute risk reduction from a 0.5% baseline VTE risk (relative risk reduction of 0.67 and number needed to treat of ~300), about 9000 women would need to be randomised. Recruiting this sample size would translate into 14 study centres enrolling at the observed rate of 13.3 patients per month during 4 years, or 20 study centres at a lower rate of 9 patients per month during 4 years. The recent multiple collaborative research efforts for COVID‐19 studies demonstrate that large multicentre studies are not only possible but also critical to answer important clinical questions [19, 20]. Although we did not formally test for a prespecific feasibility threshold, we believe that a practice‐changing clinical trial is feasible and is critically needed to inform decisions about postpartum thromboprophylaxis.
Reasons for nonparticipation among eligible women were the fear of injections, the overwhelming emotional burden of the postpartum period and the unavailability of study staff. In the literature, one qualitative study of particular interest was set in the PARTUM pilot trial, currently assessing the feasibility of low‐dose aspirin versus placebo for 6 weeks after delivery in women with low‐risk thrombophilia, immobilisation or a combination of risk factors (clinicaltrials.gov: NCT04153760). Although we await its full publication, the conference abstract highlighted many factors influencing the decision to participate: altruism, the perception of VTE risk, the birth experience and the opinion of their obstetrical care provider [21]. To improve recruitment rate of a LMWH study, we hypothesise that a reduction in treatment duration from 10 to 7 days may help, as subcutaneous injections are the #1 barrier, but the optimal duration of thromboprophylaxis is unknown. Also, a >0.5 full‐time equivalent of study midwife/nurse may decrease the proportion of women who cannot be approached due to their unavailability or that of study staff.
Oral forms of thromboprophylaxis exist, but the maternal milk excretion of direct oral anticoagulants is a critical barrier to their use [22]. The thromboprophylactic effect of low‐dose aspirin has drawn attention recently, with an estimated 30% relative risk reduction after major orthopaedic surgery or in the secondary prevention of VTE [23, 24]. We wish for the PARTUM trial to move forward to a large‐scale trial of postpartum aspirin, but strongly believe that the precise risk–benefit of low‐dose LMWH, a more powerful antithrombotic agent than aspirin, needs to be evaluated to guide and change clinical practice worldwide.
Indeed, the clinical equipoise of postpartum thromboprophylaxis exposes every year millions of young mothers to unwanted clinical outcomes. Clinical guidance and practice regarding postpartum vary tremendously [4, 6]. If LMWH is superior to no treatment, implementation efforts of postpartum LMWH would reduce the burden of postpartum VTE. If LMWH is not superior, reducing its use would decrease the burden of subcutaneous injections on postpartum women, reallocate precious health resources and possibly diminish harmful bleeding and wound outcomes [25].
4.3. Strengths and Limitations
The strengths of this pilot trial are its simple, pragmatic, open‐label characteristics, similar to a PROBE (prospective randomised open‐blinded end‐point) design. Such design is known to be scientifically robust with lower costs than a standard double‐blinded placebo‐controlled study, with a high clinical applicability [26]. Also, our study brings novel, contemporary and European data on the topic. The two main limitations are the monocentric design and the somewhat short timeframe of 6 months of this pilot trial.
5. Conclusions
In conclusion, the estimates of study acceptance and recruitment of this feasibility trial, much better than previously reported, call for the attempt to conduct a large‐scale clinical practice‐changing trial of short‐term postpartum LMWH.
Author Contributions
M.B., M.R. and B.M.D.T. designed the study. M.B., M.C. and E.C. carried out the study. M.B. analysed the data and wrote the manuscript. All authors critically revised the manuscript and approved its final version.
Conflicts of Interest
M.B. reports travel support from SOBI; B.M.D.T. reports consulting fees from Effik and Pierre‐Favre, honoraria for lectures from Effik and receipt of medical equipment from Pregnolia and Hologic; all other authors report no conflicts of interest.
Supporting information
Table S1.
Acknowledgements
With contributions from the Clinical Research Center, University Hospital and Faculty of Medicine, Geneva. Open access funding provided by Universite de Geneve.
Funding: This work was supported by PRD grant from the Geneva University Hospitals (PRD 4‐2019‐II).
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.