Symptomatic Irreversible Pulpitis (SIP)Phase 4HypertonicNCT07701551
Hypertonic Saline as a Final Flush and Post-Operative Pain After Single Visit Root Canal Treatment in Mandibular Premolar.
A Phase 4 study testing Normal (0.9%) saline and Hypertonic 3% saline in people with Symptomatic Irreversible Pulpitis (SIP), run by Cairo University.
Trial summary
This randomized controlled trial evaluates whether a final flush with 3% hypertonic saline, compared with 0.9% normal saline, reduces post-operative pain and periapical Substance P (SP) levels after single-visit root canal treatment in mandibular premolars with symptomatic irreversible pulpitis. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Symptomatic Irreversible Pulpitis (SIP)
- What is being tested?
- Normal (0.9%) saline and Hypertonic 3% saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2026to 1 Jan 2027
- Phase
- Phase 4
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-60 years, any sex
- Systemically healthy
- Mandibular premolar with clinically/radiographically diagnosed symptomatic irreversible pulpitis (prolonged, exaggerated response to cold testing; no periapical radiolucency)
- Able to use the VAS scale and complete follow-up
Who cannot join
- Medically compromised patients
- Pregnant or lactating women
- Allergy/hypersensitivity to local anesthetics or NSAIDs
- Analgesics, anti-inflammatories, or antibiotics within 12 hours pre-treatment
- Vertical root fracture, root resorption, or previous RCT
- Radiographic periapical pathology
- Non-restorable teeth
- TMD, bruxism, or traumatic occlusion interfering with pain assessment
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effect of Hypertonic Saline (3%) as a Final Flush Irrigant on Post-Operative Pain and Substance P Expression Following Single-Visit Root Canal Treatment in Patients With Symptomatic Irreversible Pulpitis Related to Mandibular Premolars: A Randomized Controlled Trial
This randomized controlled trial evaluates whether a final flush with 3% hypertonic saline, compared with 0.9% normal saline, reduces post-operative pain and periapical Substance P (SP) levels after single-visit root canal treatment in mandibular premolars with symptomatic irreversible pulpitis. Forty adult patients will be randomized 1:1. Pain will be measured with the Visual Analogue Scale (VAS) at 6, 12, 24, and 48 hours post-operatively. Periapical fluid SP levels will be measured by ELISA at two intra-operative time points (after working length determination, and after the final flush). The number of ibuprofen 400 mg tablets consumed within 24-48 hours will also be recorded.
Read the detailed description
Post-operative endodontic pain is linked to periapical release of Substance P (SP), a neuropeptide that sustains neurogenic inflammation via NK-1 receptor binding. 3% hypertonic saline has documented osmotic decongestant and NF-κB-mediated anti-inflammatory/cytokine-suppressive effects in non-dental models, providing biological rationale for its use as a final irrigant. This is a two-arm, parallel-group, participant- and assessor-blinded RCT conducted at the outpatient endodontic clinic, Faculty of Dentistry, Cairo University. After standardized access, working length determination, and a baseline periapical fluid sample (S1), canals will be shaped with continuous rotary NiTi instrumentation and irrigated with 2.5% NaOCl. After smear layer removal (2.5% NaOCl then 17% EDTA), participants receive a final flush of either 5 mL 0.9% normal saline (control) or 5 mL 3% hypertonic saline (intervention), delivered via a 30-gauge side-vented needle 2 mm short of working length. A second periapical fluid sample (S2) is then collected. Canals are obturated by lateral compaction in the same visit. Participants record VAS pain scores pre-operatively and at 6, 12, 24, and 48 hours, and log ibuprofen 400 mg tablet consumption at 24 and 48 hours. SP will be quantified from S1/S2 samples by ELISA, blinded to group allocation.
- Conditions
- Symptomatic Irreversible Pulpitis (SIP)
- Being tested
- Normal (0.9%) saline, Hypertonic 3% saline
- Keywords
- Hypertonic saline; Root canal irrigation; Substance P; Post-operative endodontic pain; Mandibular premolar; Single-visit root canal treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal (0.9%) salineDrug
Isotonic 0.9% NaCl solution used as final canal flush, no pharmacological activity
Hypertonic 3% salineDrug
Osmotic/anti-inflammatory final irrigant hypothesized to reduce periapical edema and suppress pro-inflammatory cytokine-mediated SP release via NF-κB pathway inhibition.
| Study group | Role | What they receive |
|---|---|---|
| Normal Saline 0.09 | Other | Isotonic, biologically inert final irrigant; mechanical debridement only, no pharmacological activity. Receives: Drug: Normal (0.9%) saline |
| Hypertonic Saline 3% | Experimental | Isotonic, biologically inert final irrigant; mechanical debridement only, no pharmacological activity. Receives: Drug: Hypertonic 3% saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-operative pain intensity at 6 hours
Visual Analogue Scale (VAS), 0-10 (0 = no pain, 1-3 mild, 4-6 moderate, 7-10 severe)
Measured: 6 hours post-operatively
Secondary outcomes (3)
Post-operative pain intensity at 12, 24, and 48 hours
VAS, 0-10, same categorization as primary
Measured: 12, 24, and 48 hours post-operatively
Change in periapical Substance P expression (ΔSP = S2 - S1)
Quantified by ELISA (human Substance P kit) from periapical fluid collected via paper point; pg/mL
Measured: S1 = after working length determination (intra-operative); S2 = immediately after final flush (intra-operative)
Number of rescue analgesic tablets consumed
Ibuprofen 400 mg tablets, patient-recorded tablet-count chart, max 3 tablets/24 h
Measured: 24 and 48 hours post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2026
- Study start1 Aug 2026 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Symptomatic Irreversible Pulpitis (SIP)Studies of the same condition, open and under way.
- More trials run by Cairo UniversityThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kariman Mohammed Mohammed Amin Ismaiel, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07701551
- Sponsor's protocol ID
- ENDO 3.3.3
- Acronym
- Hypertonic
- Status last verified
- Jul 2026
- First submitted
- 8 Jul 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Hypertonic Saline (3%) as a Final Flush Irrigant on Post-Operative Pain and Substance P Expression Following Single-Visit Root Canal Treatment in Patients With Symptomatic Irreversible Pulpitis Related to Mandibular Premolars: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07701551
- Acronym / sponsor ID
- Hypertonic / ENDO 3.3.3
- Conditions
- Symptomatic Irreversible Pulpitis (SIP)
- Keywords
- Hypertonic saline; Root canal irrigation; Substance P; Post-operative endodontic pain; Mandibular premolar; Single-visit root canal treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 1 Aug 2026 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 14 Jul 2026 (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.
This randomized controlled trial evaluates whether a final flush with 3% hypertonic saline, compared with 0.9% normal saline, reduces post-operative pain and periapical Substance P (SP) levels after single-visit root canal treatment in mandibular premolars with symptomatic irreversible pulpitis. Forty adult patients will be randomized 1:1. Pain will be measured with the Visual Analogue Scale (VAS) at 6, 12, 24, and 48 hours post-operatively. Periapical fluid SP levels will be measured by ELISA at two intra-operative time points (after working length determination, and after the final flush). The number of ibuprofen 400 mg tablets consumed within 24-48 hours will also be recorded.
Detailed description
Post-operative endodontic pain is linked to periapical release of Substance P (SP), a neuropeptide that sustains neurogenic inflammation via NK-1 receptor binding. 3% hypertonic saline has documented osmotic decongestant and NF-κB-mediated anti-inflammatory/cytokine-suppressive effects in non-dental models, providing biological rationale for its use as a final irrigant. This is a two-arm, parallel-group, participant- and assessor-blinded RCT conducted at the outpatient endodontic clinic, Faculty of Dentistry, Cairo University. After standardized access, working length determination, and a baseline periapical fluid sample (S1), canals will be shaped with continuous rotary NiTi instrumentation and irrigated with 2.5% NaOCl. After smear layer removal (2.5% NaOCl then 17% EDTA), participants receive a final flush of either 5 mL 0.9% normal saline (control) or 5 mL 3% hypertonic saline (intervention), delivered via a 30-gauge side-vented needle 2 mm short of working length. A second periapical fluid sample (S2) is then collected. Canals are obturated by lateral compaction in the same visit. Participants record VAS pain scores pre-operatively and at 6, 12, 24, and 48 hours, and log ibuprofen 400 mg tablet consumption at 24 and 48 hours. SP will be quantified from S1/S2 samples by ELISA, blinded to group allocation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal Saline 0.09 | Other | Drug: Normal (0.9%) salineIsotonic, biologically inert final irrigant; mechanical debridement only, no pharmacological activity. |
| Hypertonic Saline 3% | Experimental | Drug: Hypertonic 3% salineIsotonic, biologically inert final irrigant; mechanical debridement only, no pharmacological activity. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age 18-60 years, any sex
- Systemically healthy
- Mandibular premolar with clinically/radiographically diagnosed symptomatic irreversible pulpitis (prolonged, exaggerated response to cold testing; no periapical radiolucency)
- Able to use the VAS scale and complete follow-up
Key exclusion criteria (8 listed)
- Medically compromised patients
- Pregnant or lactating women
- Allergy/hypersensitivity to local anesthetics or NSAIDs
- Analgesics, anti-inflammatories, or antibiotics within 12 hours pre-treatment
- Vertical root fracture, root resorption, or previous RCT
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 |
|---|---|---|
| Normal (0.9%) salineIsotonic 0.9% NaCl solution used as final canal flush, no pharmacological activity | Drug | Normal Saline 0.09 |
| Hypertonic 3% salineOsmotic/anti-inflammatory final irrigant hypothesized to reduce periapical edema and suppress pro-inflammatory cytokine-mediated SP release via NF-κB pathway inhibition. | Drug | Hypertonic Saline 3% |
Primary outcome
Post-operative pain intensity at 6 hours
Time frame: 6 hours post-operatively
Visual Analogue Scale (VAS), 0-10 (0 = no pain, 1-3 mild, 4-6 moderate, 7-10 severe)
3 secondary outcomes
Post-operative pain intensity at 12, 24, and 48 hours
Time frame: 12, 24, and 48 hours post-operatively
Change in periapical Substance P expression (ΔSP = S2 - S1)
Time frame: S1 = after working length determination (intra-operative); S2 = immediately after final flush (intra-operative)
Number of rescue analgesic tablets consumed
Time frame: 24 and 48 hours post-operatively
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 14 Jul 2026.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Normal (0.9%) saline and Hypertonic 3% saline in people with Symptomatic Irreversible Pulpitis (SIP), run by Cairo University.
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 4 inclusion and 8 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: opening soon, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Kariman Ameen Ismaiel (+201013665586, kariman.ameen@dentistry.cu.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-operative pain intensity at 6 hours (time frame: 6 hours post-operatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jul 2026.