Pilot study on using a photometric capsule to stratify patients with suspected nonvariceal upper gastrointestinal bleeding into emergency versus elective endoscopy

Abstract

Background

Current guidelines recommend early endoscopy (within 24 hours) for hemodynamically stable patients with suspected nonvariceal upper gastrointestinal hemorrhage (NVUGIH). We evaluated the use of a new photometric capsule examination (PCE) for stratification of patients into emergency (within 12 hours) and elective (within 48–96 hours) endoscopy.

Methods

Patients with suspected NVUGIH were enrolled at four centers and received PCE. Patients with a positive capsule result (Group A) underwent emergency esophagogastroduodenoscopy (EGD) within 12 hours after admission. Patients with a negative result (Group B) received a proton pump inhibitor twice daily and underwent EGD within 48–96 hours. If signs of acute bleeding occurred in the meantime, an emergency endoscopy was performed. The primary end point was the rate of avoided early endoscopies in Group B.

Results

73 patients were included (median Glasgow–Blatchford score 11 [interquartile range 5]). In Group A (n = 32), nine patients (28.1%) were found to have active bleeding. Emergency endoscopy was avoided in 95.1%, as two patients in Group B (n = 41) received an emergency endoscopy, both without active bleeding. Two patients did not receive endoscopy and were therefore excluded from analysis. Active bleeding was excluded by PCE in the remaining 37 patients (sensitivity and negative predictive value 100%). No technical, PCE-related, or bleeding-related complications occurred during the follow-up period (30 days).

Conclusions

PCE was a quick and easy-to-use method with a high negative predictive value for suspected NVUGIH and could be used to identify patients in whom emergency endoscopy can be avoided.

Introduction

Upper gastrointestinal hemorrhage (UGIH) is one of the most common internal medicine emergencies in Western countries, with an incidence of approximately 100 per 100 000 adults per year and more than half a million hospitalizations per year in the United States [1] [2]. UGIH refers to bleeding originating from sites in the esophagus, stomach, or duodenum, the majority of which are nonvariceal upper GI bleeds (NVUGIH). Despite the availability of various assessment tools and risk scores (e.g. Glasgow–Blatchford bleeding score [GBS] or ABC score), it is often difficult to estimate the further clinical course [3] [4]. Therefore, the current guidelines recommend endoscopy within 24 hours in patients suspected of having hemodynamically stable NVUGIH in order to make a definitive diagnosis and to apply therapy if indicated [1] [5] [6]. These recommendations are supported by recent studies, which have shown that endoscopy within <6 hours, but also >24 hours, leads to a poorer prognosis [7] [8].

Therefore, performing an esophagogastroduodenoscopy (EGD) within 24 hours in patients with suspected NVUGIH is considered a key quality factor in the management of UGIH [9]. However, a recently published study (20 European centers) found that this time window is often not met, with only 59% of EGDs in UGIH being performed within 24 hours [10]. Given that early endoscopy (<24 hours) requires staff and environmental resources that may already be stretched, especially on call at weekends, there is a need for new parameters to identify patients with suspected NVUGIH in whom EGD can be safely delayed (>48 hours) [11].

Recent studies have shown that photometric capsule examination (PCE) is a rapid, easy-to-interpret, and noninvasive method for detecting blood or hematin in the upper gastrointestinal tract. This technique could therefore facilitate the decision about when to perform an emergency endoscopy [12] [13] [14] [15].

One of these capsules (HemoPill acute; Ovesco Endoscopy AG, Tübingen, Germany) has been approved for upper GI examination in Germany since 2020. Hence, we designed a prospective, multicenter, observational study to investigate whether this capsule is a proficient tool for identifying patients in whom an early endoscopy within 24 hours can be avoided.

Methods

Study design

This was a prospective, multicenter, observational study conducted at four German centers. Patients were categorized based on the PCE result and the subsequent management was observed. The primary objective was to confirm whether the use of PCE results could reliably identify patients with suspected NVUGIH in whom emergency endoscopy could be avoided. The scientific protocol, data collection sheets, and patient consent form were approved by the local ethics committee.

Photometric capsule

The photometric capsule, first described in 2019, was used to screen patients for active NVUGIH [15]. The capsule is swallowed with at least 200 mL of clear water and can be used in both fasting and nonfasting states. Capsule data are transmitted telemetrically to a receiver that is worn close to the patient’s body. The measured values (Hemopill Index, HI) are calculated using the absorption ratio of violet to red light shown as a time-dependent curve ([Fig. 1]) [13]. HI values ≥1.0 (the value set by the manufacturer) indicate the detection of blood or hematin. However, a distinction between fresh blood and hematin is not possible.

Fig. 1 The HemoPill system (Ovesco Endoscopy AG, Tübingen, Germany) consisting of recorder and capsule (size comparison: 5 euro cent coin).

Patient selection

Between October 2020 and February 2024, hemodynamically stable emergency patients referred with suspected NVUGIH (due to melena, hematin vomiting, or a drop in hemoglobin without other causes, and GBS >1) were enrolled in the study at four centers. Recruitment was hampered by various structural and organizational problems, including premature withdrawal of one center due to the departure of the study physician, significantly delayed start of recruitment in one center due to contractual problems, and recruitment only possible on weekdays (not at night or weekends) and when an inpatient bed was available. Detailed data on recruitment are provided in Table 1s in the online-only Supplementary Material. Written informed consent was obtained from each patient before capsule ingestion.

Exclusion criteria were: hemodynamic instability (heart rate >100 bpm, systolic blood pressure <100 mmHg); clinical suspicion of variceal UGIH or lower GI bleeding; hematemesis; chronic inflammatory bowel disease; severe acute and chronic organ diseases (American Society of Anesthesiologists [ASA] score ≥4); surgically altered anatomy of the upper GI tract; known or suspected gastrointestinal obstructions, strictures, fistulas or known diverticula; dysphagia or other swallowing disorders; esophageal dysmotility, gastroparesis, severe constipation; current medications for GI dysmotility; an upper GI barium study within the previous 24 hours, pacemakers, defibrillators, or other implantable electromedical devices; allergy to parylene or proton pump inhibitor (PPI); need for a prompt magnetic resonance imaging scan; and pregnancy.

Capsule application and further treatment

All patients received a PPI dose (80 mg intravenously) in accordance with the current guidelines. To minimize the influence of PPI administration on possible NVUGIH, PCE was performed within 150 minutes after PPI administration. The capsule was swallowed under medical supervision and the measured data were assessed after 120 minutes. There were no specific positioning requirements during the PCE. All patients with a positive capsule result (HI ≥1) were observed and underwent upper GI endoscopy within 12 hours (Group A). Patients with a negative result (HI <1.0) received a PPI at a standard dose twice daily, were monitored in hospital, and underwent endoscopy within 48–96 hours (Group B). If clinical or laboratory signs of acute bleeding became apparent in the meantime, an urgent endoscopy was performed.

Endoscopy

Endoscopy was performed under conscious sedation using propofol. The endoscopic findings were categorized as active, potential, or absent sources of bleeding. In addition, the type of bleeding source (ulcer, angiodysplasia, etc.) and treatment (no, yes, success) were recorded.

Follow-up

On days 28–30 after discharge, all patients were contacted by telephone to record the long-term clinical course and possible adverse events.

Study definitions and end points

Baseline patient demographics were collected, including age, sex, melena, hematin vomiting, hemoglobin drop, syncope, comorbidities, anticoagulation, blood pressure and heart rate at the time of inclusion, blood count and coagulation, blood urea, and GBS. Capsule data were assessed after 120 minutes in terms of the maximum HI value (negative <1.0; positive ≥1.0). The primary end point was the rate of avoided emergency endoscopies in the group of capsule-negative patients (extension of the time to endoscopy to at least 48 hours without acute rebleeding). This end point was specifically chosen to confirm whether PCE could effectively identify patients who could safely undergo delayed endoscopy. Secondary end points included the rate of true- and false-positive capsule results, sensitivity, and negative predictive value (NPV) regarding active bleeding, and technical success and safety of PCE.

True-positive results were defined as a capsule-positive result and active bleeding during subsequent endoscopy. A capsule-positive finding without active bleeding was considered a false-positive result. The criteria for suspected rebleeding (leading to unscheduled emergency endoscopy) were defined as: hematemesis, recurrent melena, or hematochezia after normalized bowel movement; tachycardia (≥110 bpm) or hypotension (systolic blood pressure ≤90 mmHg) without other explanation; decrease in hemoglobin value ≥2 g/dL over time without other explanation (e.g. dilution, nosebleed); no increase in hemoglobin after transfusion of packed blood cells (measured after 24 hours).

Statistical analysis

Based on previous data on PCE, we expected the rate of avoided emergency endoscopies to be 90% in the group of capsule-negative patients (Group B). A similar value was considered clinically acceptable and cost-effective in the work on video capsule endoscopy (VCE; NPV 0.92 [95%CI 0.73–0.99]) [16]. In order to achieve a similar, clinically acceptable 95%CI to that of VCE, different numbers of cases were assumed for group B. As part of an initial feasibility study with a planned recruitment period of approximately 24 months, a realistically achievable case number of 50 was assumed for Group B. Based on the above assumptions, the estimate for the primary end point (rate of avoided emergency endoscopies) was 0.9 (95%CI 0.81–0.99), which is within the range of data for VCE and was considered clinically acceptable. Based on an expected proportion of 70% capsule-negative patients in our patient population (due to initial previous experience with PCE in our clinic), the total required population for the study was determined to be 72 patients.

SPSS version 29 (IBM Corp., Armonk, New York, USA) was used for statistical analysis. The independent two-sample Student’s t test with a significance level of 5% was used in metric values. Continuous variables are summarized as mean with SD. Skewed data are presented as median and interquartile range (IQR). Categorical data were compared using Pearson’s chi-squared test and values are reported as absolute frequencies and percentages. A P value lower than 0.05 was assumed to be statistically significant. The 95%CIs were estimated as Clopper–Pearsons intervals (alpha = 0.05). Both methods were chosen as they tend to provide conservative estimates. Only patients who underwent endoscopy according to the study protocol were included in the part of the analysis that depended on endoscopically recorded parameters.

Results

Cohort characteristics

A total of 81 patients were screened for study inclusion between October 2020 and February 2024. Eight patients met the exclusion criteria (pacemaker/defibrillators or known diverticula) and were excluded after screening. Thus, a total of 73 patients (median GBS 11 [IQR 5]) with suspected NVUGIH were included after receiving an intravenous PPI dose of 80 mg. All patients received PCE within 150 minutes after PPI infusion. Using the HI threshold of 1.0, there were 32 (43.8%) positive (Group A) and 41 (56.2%) negative (Group B) capsule results. A homogeneous distribution of demographic, clinical, hemodynamic, and blood parameters was found in both groups, with the exception of blood urea, platelet count, and international normalized ratio. The transfusion rate (one or two units of packed blood cells) did not differ between groups A and B (59.4% vs. 53.7%, respectively; P = 0.78). Detailed baseline characteristics for both groups are summarized in [Table 1].

Table 1 Baseline characteristics of patients with suspected nonvariceal upper gastrointestinal bleeding who underwent photometric capsule examination to determine the timing of endoscopy.

	Group A (n = 32)1 capsule positive	Group B (n = 41)1 capsule negative	P value
GI, gastrointestinal; INR, international normalized ratio; IQR, interquartile range; (m)GBS, (modified) Glasgow–Blatchford bleeding score; PTT, partial thromboplastin time. 1Group A – endoscopy within 12 hours; Group B – endoscopy within 48–96 hours.
Age, mean (SD), years	75.2 (13.0)	70.2 (16.5)	0.16
Sex, n (%)			0.67
Male	18 (56.3)	21 (51.2)
Female	14 (43.8)	20 (48.8)
Melena, n (%)	28 (87.5)	34 (82.9)	0.75
Hematin vomiting, n (%)	3 (9.4)	6 (14.6)	0.72
Hemoglobin drop, n (%)	20 (62.5)	33 (80.5)	0.09
Syncope, n (%)	2 (6.3)	2 (4.9)	0.99
Previous GI bleeding, n (%)	5 (15.6)	11 (26.8)	0.25
Heart failure, n (%)	8 (25.0)	10 (24.4)	0.95
Liver disease, n (%)	3 (9.4)	0	0.08
Anticoagulation, n (%)	19 (59.4)	25 (61.0)	0.89
Blood pressure, mean (SD), mmHg
Systolic	132 (24)	134 (19)	0.69
Diastolic	72 (13)	69 (11)	0.33
Heart rate, mean (SD), bpm	80 (13)	81 (12)	0.70
Hemoglobin level, mean (SD), g/dL	9.1 (3.1)	8.9 (3.3)	0.77
Blood platelets, mean (SD), ×1000/µL	230 (95)	323 (126)	<0.001
INR, mean (SD)	1.22 (0.40)	1.05 (0.14)	0.024
PTT, mean (SD), seconds	29.4 (12.7)	26.3 (11.7)	0.29
Blood urea, mean (SD), mmol/L	12.9 (9.4)	8.3 (5.2)	0.016
GBS, median (IQR)	11 (6)	11 (7)	0.17
mGBS, median (IQR)	10 (5)	10 (5)	0.20

Endoscopic results and study end points

All patients in Group A (n = 32) underwent endoscopy within 12 hours after completion of the PCE (median 1.5 hours [IQR 2.5]). An active source of bleeding was identified in nine patients, with Forrest Ib ulcers being the most common finding ([Table 2], [Fig. 2]). Successful endoscopic treatment was performed in all cases. At least one potential source of bleeding was found in 18 patients (56.3%), with six findings requiring further treatment (Forrest IIa ulcer or angiodysplasia). Despite a positive capsule result, no active bleeding was found in five cases, which corresponds to a specificity of 62.9% (95%CI 44%–79%) for active bleeding ([Table 3], Table 2s).

Table 2 Endoscopic findings in patients with suspected nonvariceal upper gastrointestinal bleeding who underwent photometric capsule examination to determine the timing of endoscopy.

	Group A (n = 32)1 capsule positive	Group B (n = 39)1 capsule negative
1Group A – endoscopy within 12 hours; Group B – endoscopy within 48–96 hours.
Active bleeding source, n	9	0
Gastric
Ulcer – Forrest Ib	4	0
Duodenal
Ulcer – Forrest Ib	1	0
Angiodysplasia	1	0
Ulcer – Dieulafoy	3	0
Potential bleeding source, n	18	24
Esophagus
Erosion	0	2
Ulcer – Forrest III	0	1
Gastric
Ulcer – Forrest IIa	2	0
Ulcer – Forrest IIc	5	0
Ulcer – Forrest III	3	3
Erosion	4	13
Angiodysplasia	1	1
Cameron lesion	0	2
Duodenal
Ulcer – Forrest IIa	1	0
Ulcer – Forrest IIc	0	0
Ulcer – Forrest III	3	2
Erosion	1	0
Angiodysplasia	2	1
No bleeding source	5	15

Table 3 End points of study evaluating photometric capsule examination to determine the timing of endoscopy in patients with suspected nonvariceal upper gastrointestinal bleeding.

End point	Frequency, n/N (%)	95%CI
GI, gastrointestinal; NPV, negative predictive value; PCE, photometric capsule examination; PPV, positive predictive value.
Primary end point
Avoided emergency endoscopy	39/41 (95.1)	78–100
Secondary end points
Sensitivity for active upper GI bleeding	9/9 (100)	52–100
Specificity for active upper GI bleeding	39/62 (62.9)	44–79
PPV for active upper GI bleeding	9/32 (28.1)	9–54
NPV for active upper GI bleeding	39/39 (100)	92–100
Accuracy	48/71 (67.6)	50–82
Technical success	73/73 (100)	92–100
Adverse events related to PCE	0/6 (0)	0–8

Fig. 2 Study enrollment flow diagram. EGD, esophagogastroduodenoscopy; IV, intravenous; PO, oral; PPI, proton pump inhibitor; SAE, serious adverse event. ¹Multiple answers possible.

All patients in Group B (n = 41) received a PPI at a standard twice-daily dose. Among Group B patients, 2 underwent emergency endoscopy due to persistent hypotension (systolic blood pressure <90 mmHg). Potential sources of bleeding were found in both patients (1 cardiac tumor, 1 Forrest III ulcer), but no active bleeding. Two other patients in Group B did not undergo endoscopy (one patient refused, one patient suffered a stroke), but neither of them showed signs of bleeding during the 48-hour monitoring period. These two patients were therefore excluded from the analysis that depended on endoscopically recorded parameters. In the remaining 37 patients, EGD was performed after a median of 66.5 hours (IQR 21.0) after completion of the PCE. Active bleeding was excluded in all 37 patients, resulting in 100% sensitivity and NPV for active bleeding. Therefore, the observed proportion of patients in whom emergency endoscopy was avoided was 95.1% (95%CI 78%–100%), which aligns with the hypothesized 90% rate.

Technical success and safety

Almost all patients (72/73) swallowed the capsule with 200 mL of water without any problems. In one case, several spoons of yoghurt were also needed to swallow the capsule. The capsule measurement was completed in all patients without technical problems.

The telephone follow-up was carried out for 68 patients (93.2%) and revealed no capsule-related complications (in particular no ileus symptoms or other signs of capsule retention) or bleeding-related deaths. Detailed data on serious adverse events are provided in Table 3s.

Discussion

Endoscopy within 24 hours is the common standard in hemodynamically stable patients with suspected NVUGIH [1] [5] [6]. Nevertheless, this time interval is often not met in daily clinical practice [10].

While early endoscopy within 6 hours in hemodynamically stable patients was associated with worse outcomes (higher 30-day all-cause mortality rate, higher rate of repeat therapeutic endoscopy, and higher rate of intensive care unit admission) in a territory-wide cohort study, the data regarding late endoscopy remain unclear [7]. This Asian cohort study [7] also revealed that late endoscopy (after 24–48 hours) is associated with a worse outcome. In contrast, a large Danish cohort study found no association between outcome and timing of endoscopy in stable patients without severe comorbidities (ASA I–II) [17].

As the group of hemodynamically stable patients with suspected NVUGIH is very heterogeneous, new parameters are required to identify patients in whom late endoscopy (>48 hours) is safe. Even though the GBS offers the best clinical performance compared with other assessment systems, it cannot address this need entirely [3]. The currently established cutoff value (GBS ≤1) for outpatient treatment is safe, but not very feasible in everyday clinical practice, as most patients with suspected NVUGIH have a significantly higher GBS value. Rather, the benefit of GBS appears to be the identification of high-risk groups that require early endoscopy [18].

In addition to established clinical assessment scores, the detection of fresh blood in the upper GI tract was assumed to be an important prognostic parameter. In this context, aspiration of gastric contents (hematin/fresh blood yes/no) was abandoned due to the low sensitivity (79%) and specificity (55%) and lack of influence on the clinical outcome [19] [20].

In contrast, VCE shows better clinical data but is not a suitable emergency method due to the specialist knowledge required for evaluation [16] [21].

PCE is a new method for the rapid detection of blood or hematin in the upper GI tract and could close this important diagnostic gap. This new technology has several decisive advantages. The method is noninvasive, quick to use, and can also be performed by medical assistants without relevant training, even in the emergency room. A major advantage, especially compared with VCE, is the simple interpretation of the capsule results, with a clear limit value that can be interpreted even without special prior knowledge, whereas VCE requires specialist knowledge for evaluation [12] [15] [22] [23].

To our knowledge, two blood-detection capsule systems are currently available. The first system (HemoPill acute, used in the current study) was introduced in 2019 and showed high sensitivity for detecting blood or hematin in the upper GI tract in a prospective study [15]. Since approval in 2020, the clinical benefit of this capsule has only been investigated in a small retrospective case series [13]. Data on the second blood-sensing capsule (PillSense; EnteraSense Ltd, Galway, Ireland) was first published as a case report in 2022 [14]. A recently published prospective study with 126 patients showed high sensitivity (92.9 %) and NPV (7.8%) for blood in the upper GI tract, but the impact of this new technique on the further clinical course is still unclear [12].

Our prospective, multicenter, clinical, observational study is the first to demonstrate that the use of the new photometric capsule might have an important impact on clinical course by reliably identifying patients who do not require emergency endoscopy. This is possible due to the high sensitivity of the capsule for blood or hematin, which practically rules out active bleeding in the case of a negative capsule result. This noninvasive method makes it possible, for the first time, to identify patients who do not require emergency endoscopy despite high GBS. This is remarkable because both patient groups do not differ in their basic data and clinical parameters (especially in GBS) despite different capsule results.

To minimize potential risks for patients due to delayed endoscopy, all patients were monitored as inpatients until endoscopy, and previously established criteria were used to detect rebleeding at an early stage [24]. Based on these strict criteria, two unscheduled endoscopies were performed, which did not reveal any active bleeding. There was no relevant risk for either patient at any time, which emphasizes the high safety of the chosen concept (early elective EGD with negative capsule findings) and is reflected in the high NPV of the method. Accordingly, PCE can identify a relevant subgroup from the clinically homogeneous group of study patients with high selectivity and certainty and thus decisively change the procedure for suspected NVUGIH.

In our study, the main causes of active bleeding were Forrest Ib ulcers and Dieulafoy lesions, as well as actively bleeding angiodysplasias. Among the potential sources of bleeding, more ulcerations were found in Group A, while more erosions were found in group B, presumably due to advanced healing under the interim PPI therapy. In addition, some angiodysplasias and Cameron lesions were found among the potential sources of bleeding. Our results therefore stand in agreement with previous publications on PCE [13] [15]. In Group A, there were also five cases without a source of bleeding despite a positive capsule result; a possible explanation for this might be a self-limiting bleed from tiny aberrant vessels that were not found during the subsequent endoscopy.

As it is not technically possible to differentiate between fresh blood and hematin, we found a relevant rate of false-positive results. Therefore, the capsule is not suitable for the reliable detection of active bleeding or for situations requiring urgent (within 6 hours) endoscopic treatment. Rather, patients with a positive capsule result should undergo endoscopy within 24 hours, in accordance with current guidelines [1] [5] [6]. In addition, it should be emphasized that this study is not a randomized trial because allocation to groups A and B was based on the capsule result. Further studies (ideally as randomized noninferiority trials) should aim to overcome this limitation. Furthermore, due to the recruitment restrictions, bias in patient recruitment cannot be ruled out. Another limitation of the study is the relatively small number of cases, especially in the group with active bleeding, which may lead to a bias in the positive predictive value calculation (based on nine correct positive cases).

A serious calculation of the cost-effectiveness of PCE in the triage of upper GI bleeding is currently difficult. However, after a study on VCE (price according to the study AUD$895) showed a cost advantage in the triage of patients with upper GI bleeding, a cost advantage of the cheaper PCE (price per capsule in Germany about €160) is at least likely [16].

In summary, the new photometric capsule had a very high sensitivity for blood or hematin and could rule out active bleeding in the upper GI tract with a high degree of certainty. In this way, patients could be identified who do not require emergency endoscopy despite high GBS. As a result, personnel and financial resources could be saved, especially at weekends. Future studies should aim to investigate the above approach in a randomized design for clinical safety, including in outpatients, and to evaluate the cost-effectiveness.

Conflict of Interest

M. Brand and T. Brunk have received study funding from Ovesco Endoscopy AG. A. Kuellmer and A. Schmidt have received lecture fees and study funding from Ovesco Endoscopy AG. A. Meining is a consultant for Ovesco Endoscopy AG. G. Vogt, A. Hann, A. Weich, T. Kudlich, T. Lux, M. Weber, and E. Wedi declare that they have no conflict of interest.

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Publication History

Received: 19 December 2024

Accepted after revision: 15 June 2025

Article published online:
03 September 2025