## Protocol Section
### Identification Module
**NCT ID:** NCT06421688

**Brief Title:** Effect of Vitamin C on Postoperative Pulmonary Complications After Intracranial Tumor Surgery

**Official Title:** Effect of Vitamin C on Postoperative Pulmonary Complications After Intracranial: a Randomized, Double-blind, Placebo-controlled Study

#### Organization Study ID Info
**ID:** YXLL-KY-2024(039)
#### Organization
**Class:** OTHER
**Full Name:** Qianfoshan Hospital
### Status Module
#### Completion Date
**Date:** 2025-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-05
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Qianfoshan Hospital

#### Responsible Party

**Investigator Affiliation:** Qianfoshan Hospital

**Investigator Full Name:** Dong Wang

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

### Description Module

**Brief Summary:** The goal of this clinical trial is to investigate the effect of perioperative administration of vitamin C on postoperative pulmonary complications, with the aim of providing a safe and effective medication regimen for the prevention and treatment of postoperative pulmonary complications in patients undergoing surgery for craniocerebral tumors. The main questions it aims to answer are:

1. To determine whether vitamin C can reduce pulmonary complications after surgery for intracranial tumors.
2. Does intraoperative vitamin C improve the prognosis of surgical patients

Researchers will compare vitamin C to a placebo (saline) to see if vitamin C is effective for postoperative lung complications in patients undergoing surgery for cranial tumors.

1. Participants will be intravenously pumped with vitamin C for two hours after induction of anesthesia.
2. Participants will have intraoperative plasma sampling and recording of ventilator parameters, monitor parameters and perioperative data.
3. Participants will be followed up until discharge from the hospital to record symptoms and adverse events, and will be called at six months to check on their prognosis.

**Detailed Description:** Neurosurgery has a high incidence of postoperative pulmonary complications, increasing patient costs and affecting patient prognosis. Neurosurgery often requires hyperventilation to reduce intracranial pressure, so methods to reduce postoperative pulmonary complications such as small tidal volumes cannot be used routinely, and larger tidal volumes often result in injury to pulmonary endothelial cells, which leads to increased permeability of the pulmonary microvasculature, resulting in mechanically ventilated lung injury. Of course surgical injuries and mechanical ventilation can also cause oxidative stress injury to the lungs. Vitamin C is a common antioxidant drug and cofactor in the synthesis of many substances in the body, and many studies have shown that vitamin C prevents the increase in endothelial barrier permeability due to many causes. During the COVID-19 epidemic, vitamin C is seen as an important adjunct in preventing and ameliorating symptoms of COVID-19 patients. not only that, but vitamin C also assisted in postoperative analgesia and promote incision healing, so investigators would like to observe that by giving vitamin C during the surgery is able to prevent the occurrence of postoperative pulmonary complications or improve the prognosis of participants.

### Conditions Module

**Conditions:**

- Ascorbic Acid

- Neurosurgical Procedures

- Humans

- Ventilator-Induced Lung Injury

- Postoperative Complications

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 86

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients received 50 mg/kg of Ascorbic acid after induction of anesthesia

**Intervention Names:**

- Drug: Ascorbic acid

**Label:** Ascorbic acid group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Patients receive 50ml saline after induction of anesthesia

**Intervention Names:**

- Drug: Saline

**Label:** Control comparator group

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Ascorbic acid group

**Description:** After participants underwent induction of anesthesia, Ascorbic acid (Vitamin C Injection) was administered at a dosage of 50 mg/kg, diluted to 50 ml using saline, with a total amount not exceeding 4 g; pumping was performed using a micro pump at a rate of 25 ml/h.

**Name:** Ascorbic acid

**Other Names:**

- vitamin C

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Control comparator group

**Description:** After participants underwent induction of anesthesia, 50 ml of saline was used and pumped using a micro pump at a rate of 25 ml/h.

**Name:** Saline

**Other Names:**

- saline (medicine)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** This will be assessed using the Postoperative Pulmonary Complications Score, which ranges from 0 to 5, with a score of ≥3 being considered positive for postoperative pulmonary complications. It was assessed every day before discharge and the highest score that occurred was recorded.

**Measure:** incidence of postoperative pulmonary complications

**Time Frame:** About 10 days

#### Secondary Outcomes

**Description:** Plasma levels of neuron-specific enolase, unit is ng/ml

**Measure:** Neuron-specific enolase levels

**Time Frame:** Post operative day 1

**Description:** Length of time between participant's completion of surgery and discharge

**Measure:** Length of hospitalization

**Time Frame:** About 10 days

**Description:** PaO2/FiO2, in millimeters of mercury

**Measure:** Oxygenation index

**Time Frame:** One hour postoperative

**Description:** Patient's postoperative pain level; Using a "Pain Visual Analogue Scale", a 10-centimeter-long ruler was used, with 0 indicating no pain and 10 representing the most intense pain that was intolerable. During the test, the participant points to the scale that best represents the level of pain, and the researcher assigns the participant a score based on the location of the point.

**Measure:** Pain scores

**Time Frame:** 1 day, 3 days, 7 days postoperative

**Description:** lung compliance in Milliliter/ centimeter water column

**Measure:** pulmonary compliance

**Time Frame:** Last hour of surgery.

**Description:** The level of Interleukin-6 in the blood, in nanograms per liter

**Measure:** Interleukin-6

**Time Frame:** 1 day, 3 days, 7 days postoperative

**Description:** Blood levels of superoxide dismutase, in units per milliliter

**Measure:** superoxide dismutase (SOD)

**Time Frame:** 1 day, 3 days, 7 days postoperative

**Description:** Postoperative body temperature in degrees Celsius

**Measure:** body temperature

**Time Frame:** 1 day, 3 days, 7 days postoperative

**Description:** Systolic and diastolic blood pressure，In millimeters of mercury

**Measure:** blood pressure

**Time Frame:** About 10 days

**Description:** Plasma levels of brain-specific cardiolipin

**Measure:** Brain-specific cardiolipin

**Time Frame:** About 3 days

**Description:** Levels of neutrophils in the blood, measured in units per liter.

**Measure:** neutrophil

**Time Frame:** About 10 days

**Description:** Level of C-reactive protein in the blood in milligrams per liter

**Measure:** C-reactive protein

**Time Frame:** 1 day, 3 days, 7 days postoperative

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Patients who need craniotomy treatment due to intracranial tumors;
2. age 18-75 years old;
3. American Society of Anesthesiologists classification: 1\~3;
4. Patients and their families agree to participate in the study and sign the informed consent form.

Exclusion Criteria:

1. Patients with severe pulmonary infection or respiratory failure prior to surgery;
2. Patients with previous history of neurological or psychiatric diseases;
3. Patients with cardiac, hepatic and renal insufficiency;
4. patients who are receiving parenteral nutrition;
5. pregnant patients;
6. Patients ruled out by medication instructions;
7. Patients who require emergency surgery;
8. patients with combination of other malignant tumors;
9. patients who have participated in other clinical studies of drugs within 3 months.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ngbaise@163.com

**Name:** Dong Wang, M.D

**Phone:** 18353173516

**Role:** CONTACT

**Contact 2:**

**Email:** 2210068491@qq.com

**Name:** Linquan Shao

**Phone:** 15864548531

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Jinan

**Contacts:**

***Contact 1:***

- **Email:** ngbaise@163.com

- **Name:** Dong Wang, Doctor of Medicine(M.D.)

- **Phone:** +86-18353173516

- **Role:** CONTACT

**Country:** China

**Facility:** The First Affiliated Hospital of Shandong First Medical University

**State:** Shandong

**Zip:** 250000

#### Overall Officials

**Official 1:**

**Affiliation:** The First Affiliated Hospital of Shandong First Medical University

**Name:** Dong Wang, M.D

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** Individual Participant Data(IPD) will be available when this trial is finished and the article have been published

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Sogame LC, Vidotto MC, Jardim JR, Faresin SM. Incidence and risk factors for postoperative pulmonary complications in elective intracranial surgery. J Neurosurg. 2008 Aug;109(2):222-7. doi: 10.3171/JNS/2008/109/8/0222.

**PMID:** 18671633

**Citation:** May JM, Harrison FE. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013 Dec 10;19(17):2068-83. doi: 10.1089/ars.2013.5205. Epub 2013 May 29.

**PMID:** 23581713

**Citation:** Holford P, Carr AC, Jovic TH, Ali SR, Whitaker IS, Marik PE, Smith AD. Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients. 2020 Dec 7;12(12):3760. doi: 10.3390/nu12123760.

**PMID:** 33297491

**Citation:** Wang D, Wang M, Zhang H, Zhu H, Zhang N, Liu J. Effect of Intravenous Injection of Vitamin C on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Double-Blind, Randomized Trial. Drug Des Devel Ther. 2020 Aug 11;14:3263-3270. doi: 10.2147/DDDT.S254150. eCollection 2020.

**PMID:** 32848365

**Citation:** Costa Leme A, Hajjar LA, Volpe MS, Fukushima JT, De Santis Santiago RR, Osawa EA, Pinheiro de Almeida J, Gerent AM, Franco RA, Zanetti Feltrim MI, Nozawa E, de Moraes Coimbra VR, de Moraes Ianotti R, Hashizume CS, Kalil Filho R, Auler JO Jr, Jatene FB, Gomes Galas FR, Amato MB. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial. JAMA. 2017 Apr 11;317(14):1422-1432. doi: 10.1001/jama.2017.2297.

**PMID:** 28322416

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000013898

- Term: Thoracic Injuries

- ID: D000014947

- Term: Wounds and Injuries

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC26

- Name: Wounds and Injuries

### Condition Browse Module - Browse Leaves

- ID: M14065

- Name: Postoperative Complications

- Relevance: HIGH

- As Found: Postoperative Complications

- ID: M28143

- Name: Lung Injury

- Relevance: HIGH

- As Found: Lung Injury

- ID: M28152

- Name: Ventilator-Induced Lung Injury

- Relevance: HIGH

- As Found: Ventilator-Induced Lung Injury

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16657

- Name: Thoracic Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000055370

- Term: Lung Injury

- ID: D000055397

- Term: Ventilator-Induced Lung Injury

- ID: D000011183

- Term: Postoperative Complications

### Intervention Browse Module - Ancestors

- ID: D000014815

- Term: Vitamins

- ID: D000018977

- Term: Micronutrients

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000975

- Term: Antioxidants

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000020011

- Term: Protective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M4513

- Name: Ascorbic Acid

- Relevance: HIGH

- As Found: Heparin

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M21009

- Name: Micronutrients

- Relevance: LOW

- As Found: Unknown

- ID: M16885

- Name: Trace Elements

- Relevance: LOW

- As Found: Unknown

- ID: M4292

- Name: Antioxidants

- Relevance: LOW

- As Found: Unknown

- ID: M21869

- Name: Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: T477

- Name: Vitamin C

- Relevance: HIGH

- As Found: SARS-CoV-2

- ID: T437

- Name: Ascorbic Acid

- Relevance: HIGH

- As Found: Heparin

### Intervention Browse Module - Meshes

- ID: D000001205

- Term: Ascorbic Acid

### Misc Info Module

- Version Holder: 2024-05-31
