## Protocol Section
### Identification Module
**NCT ID:** NCT02513979

**Acronym:** PP&ARA

**Brief Title:** Postoperative Pain and Angiotensin II Receptor Antagonists

**Official Title:** The Effect of Angiotensin II Receptor Antagonists on Acute and Chronic Postoperative Pain in Patients Treated for Hypertension.

#### Organization Study ID Info
**ID:** AHSTSA-102
#### Organization
**Class:** OTHER
**Full Name:** University of Athens
### Status Module
#### Completion Date
**Date:** 2018-01

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2015-10-08

**Type:** ESTIMATED

**Last Update Submit Date:** 2015-10-07

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2017-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2015-08

**Status Verified Date:** 2015-07

#### Study First Post Date
**Date:** 2015-08-03
**Type:** ESTIMATED
**Study First Submit Date:** 2015-07-28
**Study First Submit QC Date:** 2015-07-30
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Athens

#### Responsible Party

**Investigator Affiliation:** University of Athens

**Investigator Full Name:** Argyro Fassoulaki

**Investigator Title:** Professor Emeritus

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** An angiotensin II type 2 receptor (AT2R) antagonist has been assessed for its efficacy in neuropathic pain with promising results. A considerable number of patients undergoing surgery under general anesthesia are hypertensive and receive drugs to control high blood pressure, including angiotensin II receptor antagonists. These drugs may attenuate the acute and/or chronic postoperative pain or decrease the analgesic requirements after surgery. The aim of the present study is to assess the early postoperative pain and analgesic requirements in patients treated with antagonists of the angiotensin II receptors for at least three months before surgery compared to normotensive patients.

**Detailed Description:** Patients ASA I-III, aged between 35 and 79 years old, with BMI ≤ 35, scheduled for abdominal surgery, thus gynecological, urological and general surgery procedures will be recruited for the study. All patients will be scheduled in the morning list, informed for the study and will be asked to give written informed consent.

Exclusion Criteria will be patients on analgesic, antidepressive, or sedative consumption during the previous one month, mental impairment, not speaking Greek or refusing to give written informed consent, diabetics, patients receiving antihypertensive treatment other than angiotensin type II receptor (AT2R) antagonists.

Two groups of patients will be stydied: Patients hypertensive (the hypertensive group) receiving treatment for blood pressure control with angiotensin II receptor antagonists for at least three months preoperatively and a normotensive group.

Measurements

* Pain intensity (visual analogue scale: VAS) from 0 to 100 will be reported 2, 4, 8, and 24 hours postoperatively with 0 representing no pain and 100 excruciate worst pain. Pain will be recorded at rest and subsequently patients will be asked to cough for three times.
* Analgesics consumed at the same time points will be recorded.
* Patient satisfaction (VAS 0-100) 24 h postoperatively (with special reference to pain)
* Three months postoperatively patients will be contacted by phone and will be asked if they experience pain related to surgery or not. If yes pain characteristics, thus burning, pricking etc. will be recorded.
* Three months postoperatively patients will be asked whether they used analgesics after discharge from the hospital for the postoperative pain.

Statistics Primary outcome of the study: Pain intensity 24 hours postoperatively after cough in patients receiving angiotensin II receptor antagonists, or no antihypertensive therapy. Secondary outcomes of the study are pain intensity 2, 4, 8 and 24 hours postoperatively at rest, 2, 4 and 8 hours after cough, analgesic consumption , 2, 4, 8 and 24 hours postoperatively, patient satisfaction regarding pain, presence of pain three months after surgery and if present its characteristics. Also, analgesic consumption during the first three months postoperatively due to surgery.

Statistics Power analysis: A 30% difference in pain intensity after cough 24 hours postoperatively between the angiotensin II receptor antagonists treated group compared and the treated group.

Acute pain at rest and after cough all the time points as defined by the study design will be compared between patients receiving antihypertensive treatment (angiotensin II receptors antagonists) and the controls.

Cumulative analgesics consumed 2, 4, 8 and 24 hours after surgery will be compared between the two groups.

The presence of chronic postsurgical pain and the need or not of analgesic intake due to chronic pain three months after surgery will be also compared between the hypertensive treated and normotensive patients.

Parametric or non-parametric tests will be used for normal and no normal distributions respectively.

### Conditions Module

**Conditions:**

- Hypertension

**Keywords:**

- Angiotensin type II receptor (AT2R) antagonists

- Acute postoperative pain

- Chronic postoperative pain

- Abdominal surgery

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 90

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Hypertensive patients treated with angiotensin type II receptor antagonists

**Intervention Names:**

- Drug: Angiotensin type II receptor antagonists

**Label:** angiotensin type II receptor antagonists

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Normotensive patients

**Label:** No treatment

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- angiotensin type II receptor antagonists

**Description:** Angiotensin type II receptor antagonists given to hypertensive patients treated with high blood pressure

**Name:** Angiotensin type II receptor antagonists

**Other Names:**

- AT2R antagonists

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Patient satisfaction measured in a 0-100 mm scale with special reference to postoperative pain management

**Measure:** Patient satisfaction

**Time Frame:** 24 hours postoperatively

#### Primary Outcomes

**Description:** Intensity of pain after cough measured with the Visual Analogue Scale (VAS 0-100 mm)

**Measure:** Acute pain after cough

**Time Frame:** 24 hours postoperatively

#### Secondary Outcomes

**Description:** Intensity of pain at rest measured with the Visual Analogue Scale (VAS 0-100 mm)

**Measure:** Acute pain at rest

**Time Frame:** 2, 4, 8 and 24 hours postoperatively

**Description:** Intensity of pain after cough measured with the Visual Analogue Scale (VAS 0-100 mm)

**Measure:** Acute pain after cough

**Time Frame:** 2, 4 and 8 hours postoperatively

**Description:** All analgesics converted to morphine equivalent (mg)

**Measure:** Analgesic consumption

**Time Frame:** 2, 4, 8 and 24 hours postoperatively

**Description:** Present or absent, if present characteristics (pricking, burning, throbbing)

**Measure:** Chronic pain

**Time Frame:** Three months postoperatively

**Description:** Yes or not, number of pills

**Measure:** Analgesic consumption for chronic pain

**Time Frame:** Three months postoperatively

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Patients aged between 35 and 79 years
* ASA II or III
* BMI ≤ 35
* Elective abdominal surgery Exclusion Criteria:-
* Patients on analgesic, antidepressive, or sedative consumption during the last month
* Mental impairment
* Not speaking fluently Greek language
* Refuse to give written informed consent
* Diabetics
* Patients receiving antihypertensive treatment other than angiotensin type II receptor (AT2R) antagonists

**Maximum Age:** 79 Years

**Minimum Age:** 35 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** afassou1@otenet.gr

**Name:** Argyro Fassoulaki, MD, PhD

**Phone:** +30210 9024530

**Role:** CONTACT

**Contact 2:**

**Email:** mariavalta@yahoo.com

**Name:** Maria Valta, MD

**Phone:** +30210 8062133

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Athens

**Contacts:**

***Contact 1:***

- **Email:** fassoula@aretaieio.uoa.gr

- **Name:** Argyro Fassoulaki, MD, PhD

- **Phone:** +30 6936701333

- **Role:** CONTACT

***Contact 2:***

- **Email:** mariavalta@yahoo.com

- **Name:** Maria Valta, MD

- **Phone:** +30 6971554146

- **Role:** CONTACT

**Country:** Greece

**Facility:** Argyro Fassoulaki

**Status:** RECRUITING

**Zip:** 11528

#### Overall Officials

**Official 1:**

**Affiliation:** Aretaieio University Hospital

**Name:** Argyro Fassoulaki, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** St Savas Hospital

**Name:** Marianna Zotou, MD

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000011183

- Term: Postoperative Complications

- ID: D000010335

- Term: Pathologic Processes

- ID: D000010146

- Term: Pain

- ID: D000009461

- Term: Neurologic Manifestations

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M13069

- Name: Pain, Postoperative

- Relevance: HIGH

- As Found: Postoperative Pain

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: Hypertension

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14065

- Name: Postoperative Complications

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006973

- Term: Hypertension

- ID: D000010149

- Term: Pain, Postoperative

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaCoAg

- Name: Vasoconstrictor Agents

### Intervention Browse Module - Browse Leaves

- ID: M28916

- Name: Angiotensin Receptor Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M4132

- Name: Angiotensin II

- Relevance: LOW

- As Found: Unknown

- ID: M289354

- Name: Giapreza

- Relevance: LOW

- As Found: Unknown

- ID: M4135

- Name: Angiotensinogen

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
