Achalasia CardiaRECAPNCT07022886
INCIDENCE, PREVALENCE AND OVERALL RISK OF ESOPHAGEAL CANCER IN ACHALASIA: A PROPENSITY-MATCHED POPULATION-BASED STUDY FROM A LARGE MULTICENTER DATABASE
An observational study of Achalasia Cardia and Esophageal Cancer (EsC), run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Esophageal Achalasia has been investigated as a potential risk factor for esophageal cancer (EC). Longstanding disease, repeated treatment, age and male sex seem the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Achalasia Cardia, Esophageal Cancer (EsC)
- What is being tested?
- achalasia treatments
- Type of treatment
- Surgery or procedure
- How many people
- 47,000 participants
- Where
- 1 siteItaly
- Study dates
- 3 Jun 2025to 7 Sep 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Achalasia diagnosis according to guidelines as stated in Electronic Health Records (EHR) data.
Who may be able to join
- Esophageal achalasia diagnosed according to guidelines (ICD-10-K22.0)
Who cannot join
- Primary esophaeal and pharyngeal motility disorders (ICD-10-J39.2)
Trial locations and contacts
1 site in 1 country.
About this study
Esophageal Achalasia has been investigated as a potential risk factor for esophageal cancer (EC). Longstanding disease, repeated treatment, age and male sex seem the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far. The aim of the investigators is to estimate EC risk in large sample-size population, and to provide sub-analyses per cancer type and treatment impact on EC risk.
Read the detailed description
Achalasia is a chronic idiopathic condition characterized by the absence of esophageal peristalsis and reduced relaxation of the lower esophageal sphincter, causing progressive dysphagia and weight loss. Achalasia has been investigated as a potential risk factor for esophageal cancer (EC); squamous cancer due to chronic inflammation related to stasis due to poor esophageal emptying and adenocarcinoma due to uncontrolled gastroesophageal reflux after treatment. Longstanding disease, repeated treatment, age and male sex have been addressed as the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far.
The authors conducted a retrospective cohort study, accessing the global federated health research network "TriNetX", that provides access to electronic medical records from approximately a hundred million patients across large healthcare organizations (HCOs). The analysis will be performed on achalasia patients, based on the ICD-10 code (K22.0), from January 1st 2000 until May 31st 2025. The incidence rate (cases/1000 persons-year) and cumulative prevalence of EC in an achalasia cohort in a span of 25 years will be firstly assessed. Then the absolute and time-to-event risk of EC, by comparing the achalasia cohort with control cohort, after propensity score nearest neighbor greedy matching, for relevant covariates. Kaplan-Meyer (KM) analysis with censoring, Hazard Ratios (HRs) and Risk Ratio (RR) and Risk Difference (RD) estimation for EC risk will be calculated. Log Rank test will be used to compare KM curves. Further sub-group analysis will be implemented between two population of achalasia patients, treated (with endoscopic/surgical myotomy or pneumatic dilation) and treatment-naïve. Further in-depth analyses between histologic type of EC, esophageal localization and comparing different achalasia treatment (myotomy vs pneumatic dilation) will be performed, in order to categorize the risk of EC, if more linked to treatment and therefore to the development of reflux, Barrett esophagus eventually leading to adenocarcinoma, or towards squamous cell cancer driven by chronic stasis and degeneration of the squamous esophageal epithelium
- Conditions
- Achalasia Cardia, Esophageal Cancer (EsC)
- Being tested
- achalasia treatments
- Keywords
- achalasia, esophageal cancer
- Medical subject headings
- Esophageal Achalasia, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
achalasia treatmentsProcedure or surgery
Also called POEM, LHM
esophageal achalasia treatments
| Study group | Role | What they receive |
|---|---|---|
| Achalasia primary cohort | Achalasia cohort (both naive or treated) | |
| Control subjects | Healthy controls, with the exclusion of achalasia | |
| Achalasia without Barrett Esophagus | Sensitivity analysis of achalasia both treated or untreated without Barrett esophagus | |
| Treated achalasia | achalasia undergone to various treatments Receives: Procedure: achalasia treatments | |
| Untreated achalasia | Achalasia without previous treatment | |
| LHM | Heller-Dor myotomy Receives: Procedure: achalasia treatments | |
| POEM | Peroral endoscopic myotomy Receives: Procedure: achalasia treatments |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hazard Ratio
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence in achalasia vs control subjects
Measured: from Jan 1st 2000 to June 3rd 2025
Incidence proportion, prevalence and incidence rate
Incidence proportion (%), prevalence (%) and incidence rate (100,000 persons-year) of EC (and different histological subtypes)
Measured: Jan 1st 2000- June 3rd 2025
Secondary outcomes (3)
Risk Ratio
Risk Ratio of EC (and different histologic subtypes) occurrence in achalasia cohort compared to controls, in treated vs untreated achalasia, LHM vs POEM group
Measured: Jan 1st 2000-Jun 3rd 2025
Risk Difference
Risk Difference of EC (and different histological subtypes) occurrence in achalasia cohort compared to controls, in treated vs untreated achalasia, LHM vs POEM group
Measured: Jan 1st 2000-June 3rd 2025
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence (according to different subtypes) in achalasia vs control subjects and in treated vs untreated achalasia, and in LHM vs POEM
Measured: Jan 1st 2000- June 3rd 2025
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2025
- Study start3 Jun 2025
- Primary completion3 Jun 2025
- Study completion7 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Achalasia CardiaStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 47,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- TriNetX, LLC, Università Vita-Salute San Raffaele
- Responsible party
- Principal investigator, Alberto Barchi, IRCCS San Raffaele
- Investigators
- Albert Jan Bredenoord, MD, PhD, Prof, Study director, Department of Gastroenterology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07022886
- Sponsor's protocol ID
- RECAP
- Acronym
- RECAP
- Status last verified
- Jul 2025
- First submitted
- 8 Jun 2025
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD used in this study
Publications
Ponds FA, Moonen A, Smout AJPM, Rohof WOA, Tack J, van Gool S, Bisschops R, Bredenoord AJ, Boeckxstaens GE. Screening for dysplasia with Lugol chromoendoscopy in longstanding idiopathic achalasia. Am J Gastroenterol. 2018 Jun;113(6):855-862. doi: 10.1038/s41395-018-0064-1.
PubMed 29748564Tustumi F, Bernardo WM, da Rocha JRM, Szachnowicz S, Seguro FC, Bianchi ET, Sallum RAA, Cecconello I. Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis. Dis Esophagus. 2017 Oct 1;30(10):1-8. doi: 10.1093/dote/dox072.
PubMed 28859394Gillies CL, Farrukh A, Abrams KR, Mayberry JF. Risk of esophageal cancer in achalasia cardia: A meta-analysis. JGH Open. 2019 Feb 8;3(3):196-200. doi: 10.1002/jgh3.12132. eCollection 2019 Jun.
PubMed 31276035
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INCIDENCE, PREVALENCE AND OVERALL RISK OF ESOPHAGEAL CANCER IN ACHALASIA: A PROPENSITY-MATCHED POPULATION-BASED STUDY FROM A LARGE MULTICENTER DATABASE
- ClinicalTrials.gov ID
- NCT07022886
- Acronym / sponsor ID
- RECAP / RECAP
- Conditions
- Achalasia Cardia, Esophageal Cancer (EsC)
- Keywords
- achalasia, esophageal cancer
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 47,000 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- TriNetX, LLC, Università Vita-Salute San Raffaele
- Study start
- 3 Jun 2025 (actual)
- Primary completion
- 3 Jun 2025 (actual)
- Study completion
- 7 Sep 2025 (estimated)
- First posted
- 15 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Esophageal Achalasia has been investigated as a potential risk factor for esophageal cancer (EC). Longstanding disease, repeated treatment, age and male sex seem the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far. The aim of the investigators is to estimate EC risk in large sample-size population, and to provide sub-analyses per cancer type and treatment impact on EC risk.
Detailed description
Achalasia is a chronic idiopathic condition characterized by the absence of esophageal peristalsis and reduced relaxation of the lower esophageal sphincter, causing progressive dysphagia and weight loss. Achalasia has been investigated as a potential risk factor for esophageal cancer (EC); squamous cancer due to chronic inflammation related to stasis due to poor esophageal emptying and adenocarcinoma due to uncontrolled gastroesophageal reflux after treatment. Longstanding disease, repeated treatment, age and male sex have been addressed as the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far.
The authors conducted a retrospective cohort study, accessing the global federated health research network "TriNetX", that provides access to electronic medical records from approximately a hundred million patients across large healthcare organizations (HCOs). The analysis will be performed on achalasia patients, based on the ICD-10 code (K22.0), from January 1st 2000 until May 31st 2025. The incidence rate (cases/1000 persons-year) and cumulative prevalence of EC in an achalasia cohort in a span of 25 years will be firstly assessed. Then the absolute and time-to-event risk of EC, by comparing the achalasia cohort with control cohort, after propensity score nearest neighbor greedy matching, for relevant covariates. Kaplan-Meyer (KM) analysis with censoring, Hazard Ratios (HRs) and Risk Ratio (RR) and Risk Difference (RD) estimation for EC risk will be calculated. Log Rank test will be used to compare KM curves. Further sub-group analysis will be implemented between two population of achalasia patients, treated (with endoscopic/surgical myotomy or pneumatic dilation) and treatment-naïve. Further in-depth analyses between histologic type of EC, esophageal localization and comparing different achalasia treatment (myotomy vs pneumatic dilation) will be performed, in order to categorize the risk of EC, if more linked to treatment and therefore to the development of reflux, Barrett esophagus eventually leading to adenocarcinoma, or towards squamous cell cancer driven by chronic stasis and degeneration of the squamous esophageal epithelium
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Achalasia primary cohort | – | –Achalasia cohort (both naive or treated) |
| Control subjects | – | –Healthy controls, with the exclusion of achalasia |
| Achalasia without Barrett Esophagus | – | –Sensitivity analysis of achalasia both treated or untreated without Barrett esophagus |
| Treated achalasia | – | Procedure: achalasia treatmentsachalasia undergone to various treatments |
| Untreated achalasia | – | –Achalasia without previous treatment |
| LHM | – | Procedure: achalasia treatmentsHeller-Dor myotomy |
| POEM | – | Procedure: achalasia treatmentsPeroral endoscopic myotomy |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Achalasia diagnosis according to guidelines as stated in Electronic Health Records (EHR) data.
Key inclusion criteria (1 listed)
- Esophageal achalasia diagnosed according to guidelines (ICD-10-K22.0)
Key exclusion criteria (1 listed)
- Primary esophaeal and pharyngeal motility disorders (ICD-10-J39.2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| achalasia treatmentsAlso: POEM, LHMesophageal achalasia treatments | Procedure or surgery | LHM, POEM, Treated achalasia |
Primary outcome
Hazard Ratio
Time frame: from Jan 1st 2000 to June 3rd 2025
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence in achalasia vs control subjects
Incidence proportion, prevalence and incidence rate
Time frame: Jan 1st 2000- June 3rd 2025
Incidence proportion (%), prevalence (%) and incidence rate (100,000 persons-year) of EC (and different histological subtypes)
3 secondary outcomes
Risk Ratio
Time frame: Jan 1st 2000-Jun 3rd 2025
Risk Difference
Time frame: Jan 1st 2000-June 3rd 2025
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence
Time frame: Jan 1st 2000- June 3rd 2025
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
- Background: PubMed 29748564Ponds FA, Moonen A, Smout AJPM, Rohof WOA, Tack J, van Gool S, Bisschops R, Bredenoord AJ, Boeckxstaens GE. Screening for dysplasia with Lugol chromoendoscopy in longstanding idiopathic achalasia. Am J Gastroenterol. 2018 Jun;113(6):855-862. doi: 10.1038/s41395-018-0064-1.
- Background: PubMed 28859394Tustumi F, Bernardo WM, da Rocha JRM, Szachnowicz S, Seguro FC, Bianchi ET, Sallum RAA, Cecconello I. Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis. Dis Esophagus. 2017 Oct 1;30(10):1-8. doi: 10.1093/dote/dox072.
- Background: PubMed 31276035Gillies CL, Farrukh A, Abrams KR, Mayberry JF. Risk of esophageal cancer in achalasia cardia: A meta-analysis. JGH Open. 2019 Feb 8;3(3):196-200. doi: 10.1002/jgh3.12132. eCollection 2019 Jun.
- TriNetX platform linkLink provided by the sponsor.
- Individual participant dataSharing planned: No. No IPD used in this study
Related trials for Achalasia Cardia
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
Full-thickness Versus Progressive Myotomy in Peroral Endoscopic Esophageal Myotomy in Achalasia: A Randomized Controlled Trial
Achalasia Cardia, Achalasia
RecruitingPhase 3
PREcision MEDicine In Achalasia (PREMEDIA)
Type I Achalasia, Type II Achalasia
RecruitingObservational study
PREcision MEDicine In Achalasia (PREMEDIA) - Cohort
Type III Achalasia, EGJ Outflow Obstruction With Spastic/Hypercontractile Features
RecruitingPhase 4
VZV in the Enteric Nervous System: Pathogenesis and Consequences
Achalasia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Jan Bredenoord, MD, PhD, Prof study director
Department of Gastroenterology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Achalasia Cardia and Esophageal Cancer (EsC), run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hazard Ratio (time frame: from Jan 1st 2000 to June 3rd 2025). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07022886, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.